SLA Biomedical & Life Sciences Division Blog

Statins Score a Major Success as A Preventive Prescription Even for Those Patients at Seemingly Low Risk of Heart Disease & Stroke, Excepting that They Have a High C-Reactive Protein Level: Confirming the Value of Statins While Spotlighting CRPs

The blog of September 12, 2008,  had the rambling title of: “To avoid any long-term risk from taking statins, should you stop and die surer and sooner from cardiovascular disease? An old controversy flares up again over the most successful class of heart medicines in history.”

Its main point was that relatively isolated research setbacks reported in the popular media, and somewhat far-fetched cancer fears that go back to the distant discovery of statins, should not likely discourage doctors from a consideration of carefully prescribing and monitoring the use of this class of drugs, the statins, for their patients, because the medical literature overwhelmingly showed a wonderful benfit:risk ratio.

The New York Times today ( Monday, November 10, 2008, vol.158 (54490): A1,A19) featured a front-page account  by Pam Belluck providing us a strongly pro-statin use study conducted by Ridker et al of the JUPITER collaboration: Justification for the Use of Statins in Prevention:  an Intervention Trial Evaluating Rosuvastatin. 

(Rosuvastatin is the generic name for the brand name drug Crestor™.)

The study and an accompanying editorial by (Hlatky 2008, see below) were very clear: after taking the rosuvustatin as directed, there was a substantial reduction (50%) in the malevolent low-density cholesterol, a dramatic result.

Further, there was a clear cut decrease of approximately 20% in heart attacks, 50% in strokes, and a greatly decreased number of patients who needed bypass surgery or were hospitalized for unstable angina.

There was neither the alleged muscle weaknesses found in a small number of cases with other statins, nor was there any greater risk of developing cancer. (The cancer rate was actually marginally lower with rosuvastatin!)

However, the rate of increase in diabetes marginally increased, although it is not clear within this cohort, that some of the patients were not already in prime temporal territory for adult onset diabetes any way.

The study involved 17,802 patients, men in their 50s and women in their 60s, half of whom took placebos while the remainder took the rosuvastatin in the standard 20 mg. dosages.

The patients were selected for the study  for two reasons.

First, they were without adverse serious low-density cholesterol or triglyceride blood counts, and had no history of heart, vascular or cerebrovascular illnesses, such as infarcts, a need for coronary bypass grafts, or any strokes. In many cases they were assessed as having a Framingham Heart Disease study risk scores of 10% or less, a virtually optimal heart-healthy statistical category.

Second, they had to have high values for C-reactive proteins in their bloodstream.

C-reactive proteins are thought to be indicative, but not necessarily causative, of a wide variety of illness. More than anything else, they are seen as biomarkers of inflammation going on somewhere in the body.

They are associated strongly with Type II diabetes, and with metabolic syndrome, both of which are also associated with an increased risk of heart disease and stroke.

C-reactive proteins are also elevated in people with obstructive sleep apnea, and people who had a diet that included significant amounts of trans-fats. These are also pre-disposers to heart attacks and stroke.

C-reactive proteins are also associated with fatty livers, both those seen in alcoholics and in some other rather rarer conditions. Inboth caases, those patients are also at higher disease for heart attacks and stroke.

C-reactive proteins are plentiful in people suffering from atrial fibrillation, a dangerous mis-patterning of the sinus-wave in their heart rhythms. People who have had coronary bypass surgery, or who had their hearts “shocked” back into a normal sinus rhythm, can be tested to see if they are likely  revert to erratic heart beatings through measuring the level of C-reactive protein. Higher levels means a higher likelihood of relapse.

But curiously, higher levels of C-reactive proteins are also found in patients with autoimmune disorders such as psoriasis, rheumatoid arthritis, and lupus. It might be less well known that especially in the case of lupus, heart and stroke risk for these patients might be higher than normal for age, weight and other indicators.

In many ways, today’s blog strengthen the general case for the continued use of statins in their various formulations. A greater consensus will probably have to be built as to what level of C-reactive proteins should be the trigger for prescribing rosuvastatin. 

But just as certainly, the study of C-reactive proteins will intensify further as well.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              

Ctirad A et al. Goeckerman’ therapy for psoriasis with special reference to serum pentraxin 3 level. International Journal of Dermatology 47 (10): 11-14.

Deghan A. et al. 2007. Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes  56 (3): 872-878.

Deghan A et al. 2007. Risk of type 2 diabetes attributable to C-reactive protein and other risk factors.  Diabetes Care 30 (10): 2695-2699.

Hlatky MA. 2008. Expanding the orbit of primary prevention – Moving beyond JUPITER. New England Journal of Medicine 359 (21): 2280-2283.

Howard PA & Barnes BJ. 2008. Potential use of statins to prevent atrial fibrillation after coronary bypass surgery.  Annals of Pharmacotherapy 42 (2) 253-258.

Kapsimalis F. et al. 2008. Association of sleep apnea severity and obesity with insulin resistance protein, and leptin levels in male patients with obstructive sleep apnea. Lung 186 (4): 209-217.

Lau DC et al. 2005. Adipokines: Molecular links between obesity & atherosclerosis. American Journal of Physiology: Heart & Circulatory Physiology 288 (5): H2031-H2041.

Lavie CJ, Morshedi-Meibodi A, Milani RV. 2008. Impact of cardiac rehabilitation on coronary risk factors, inflammation, and the metabolic syndrome. Journal of Cardiometalobic Syndrome 3 (3): 136-140.

Liu T et al. 2007. Association between C-reactive protein and recurrence of atrial fibrillation after successful cardioversion: A meta-analysis. Journal of the American College of Cardiology 49 (15): 1649-1650.

Lopez-Garcia E. 2005. Consumption of trans-fatty acids is related to plasma biomarkers of inflammation & endothelial function. Journal of Nutrition 135 (3): 562-566.

Pepys MB & Hirschfield GM. 2003. C-Reactive protein: A critical update. Journal of Clinical Investigation

Polotsky VY et al. 2008. Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity. American Journal of Respiratory & Critical Care Medicine e-pub ahead of print posted October 31. v. 178

Poole  CD et al. The association between C-Reactive protein and the likelihood of progression to joint replacement in people with rheumatoid arthritis:  A retrospective observational study. BMC Musculoskeletal Disorders 9 (1): 146.

Ridker PM et al.  2008. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. New England Journal of Medicine 359 (21): 2195-2207.

Smith KM et al. 2008. Relationship between fish intake, n-3 fatty acids, mercury & risk markers of CHD from the National Health & Nutrition Survey. Public Health Nutrition 6: 1-9.

Tony Stankus [email protected] Life Sciences Librarian

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

That Other 2008 Nobel Prize in Medicine: This Year’s Chemistry Laureates Illuminate the BioMedical & Life Sciences on the Pages of Some of the Most Important Journals in Our Field.

A few weeks back this blog covered the the journals which were most important to the winners of the 2008 Nobel Prizes in Medicine which went to three important virologists, Francoise Barre-Sinoussi & Luc Montagnier for their discovery of the AIDS virus, and Harald zur Hausen for the discovery of the human papilloma viruses that cause many cases of cervical cancer.

This year’s chemistry prizes could well have qualified under the physiology and medicine category, and one of this year’s three  recipients, Osamu Shimomura, emeritus professor and researcher at Boston University  and Marine Biological Laboratories on Cape Cod, actually told reporters that he knew he was in the running for the prize in medicine, and   was quite surprised that he got it in chemistry instead.

He has not, however, made any plans to return it and wait for next year’s in medicine instead.

The other two co-recipients Martin Chalfie of Columbia University in New York City, and Roger Tsien of U. Cal., San Diego, were   just as likely candidates for the prize in medicine, because what they did is used far more by biologists and medical researchers rather than by chemists of most types.

Their collective contribution was in developing small protein tags that could be attached harmlessly to other larger proteins, by way of a tracer, albeit one with a vitally important advantage that will be discussed shortly.

This year’s chemistry Nobel Prize is an homage to an almost 300 year old field called stain technology or histochemistry,   and to the  102^nd anniversary of the first Nobel Prize awards in this area, given to the Italian researcher Camillo Golgi, and to his Spanish contemporary Ramon y Cajal,  a medical professor who might be described as one of the first neurologists.

Whether one wishes to credit Antonie  van Leeuwenhoek ( 1632-1723), a Dutch inspector of cloth weaves whose hobby was biology, who used  an open single lens design that actually allowed for better color vision, or Robert Hooke (1635-1703), an English scientist of a many great talents (and one even  greater enemy, Isaac Newton), who invented the tubular design overwhelmingly used today, as the true founder of biological microscopy, it can be agreed upon that they and their successors would eventually be limited by same great problem with early microscopy.

This was not any fundamental limitation on achieving greater and greater magnification (that would take another 200 years), but rather the  increasing difficulty of visualizing the increasingly tiny structures within cells which appeared so translucent as to be invisible under strong  microscopic magnification  and intense illumination. 

This “invisible man” problem was solved on a case by case basis for each particular type of specimen by the injection or immersion of the sample in chemicals or food dyes that stained the desired structures.

These might enable, for example, a cell’s nucleus to stand out, or help delineate the layers in cell walls.

Several thousands of these were developed, but at first, not many of them were able to be used across many different types of specimens.

Progress came when either a particularly versatile stain was developed or something that resisted staining finally yielded to the right combination of trial and error.

Such was the case of those early Nobel laureates Camillo Golgi, who used silver stains to discover the hitherto undetected and surprisingly complex cellular  structure how called the Golgi body, and Ramon y Cajal who adapted Golgi’s silver stains, to finally delineate and trace single nerve cells in the brain, spinal cord, and limbs.

These stains, and the vast majority of others, however, actually killed the cells so the resulting image was static, and told the scientist more about altered structures rather than about altered physiology. This was still progress since many diseases involve alteration of expected cellular structure, particularly the various types of cancer.

But a tiny handful of histochemicals allowed the cell to keep on living, for at least a short time, so that a small range of normal and abnormal physiological processes   could be observed. 

It is in this category that the works of Shimomura, Chalfie and Tsien fall. 

Using an observation in marine biology, about  certain jellyfish which glowed just by being exposed to different kinds of light,  they were able to:

·        Find the particular proteins that did the glowing, initially a type called Green Fluorescent Protein or GFP for short.

·        And then, with a coworker , Douglas C. Prasher, (who actually recently  left science under dire economic circumstances with concurrent bouts of clinical depression, and now drives a shuttle van for a car dealer repair shop) found the genes that directed the production of the proteins that enabled the glowing.

·        And then develop processes for incorporating the genes that  made the glow proteins,  into  a parts of a living organism

·        And developed different genetic and therefore  protein peptide sequences which yielded different colors

·        That glowed in ways that illuminated  specific cellular functions, with different colors glowing at the same time as demonstrations of different, simultaneous activities going on in living cells.

We will now survey the journals that mattered most to these scientists. Once again we will use Thomson-Reuter’s Web of Science, realizing that other databases might provide somewhat different article counts, but that these are not likely to change significantly the trends we observe and celebrate in these authors.

Osamu Shimomura

Shimomura is the oldest of the laureates (80) and in many respects his record   shows the most deference to journals that have long been of value to biochemistry and cell biology for decades, and in some cases, for almost a century. A scientist whose training included periods in both Japan and America, he shows himself to be among the most international  in his choice of venues for his research.

His favorite outlet has been the British-based, 1906- established Biochemical Journal (11 papers), this is not entirely a surprise in that many East Asian scientists had at least as great a familiarity with that title as with its principal American competitor, the Journal of Biological Chemistry ( where he has never published, more surprisingly).

Other  biochemistry titles include FEBS Letters from Elsevier and the Federation of European Biochemical Societies (7 papers), a post WW II journal that is intentionally international, as are most of his other choices, most particularly Elsevier’s Biochimica et Biophysica Acta the home of a paper that came out just this May, 2008.

One of his more important mini-reviews has also appeared in another  Elsevier title, Trends in Biochemical Sciences.

American-based but long sharing British and Dutch Editors is Comparative Biochemistry & Physiology ( 8 papers). It is another Elsevier title in biochemistry, albeit one where the stress is as much on the role the discussed biochemical plays in the life of the organism from which it came. It makes a great deal of sense in Shimomura’s assortment, since the luminescent proteins he explored largely came from luminescent marine organisms, where their role is a matter of much speculation. 

Similarly US-based, but international of authorship and often of editorship,  are Analytical Biochemistry (3 papers), and Biochemical & Biophysical Research Communications (3 papers). Since the fluorescent proteins he discovered are particularly good at indicating the flow of metabolically important minerals and ions, the two papers in Cell Calcium make considerable sense, as does his paper in Protein Expression & Purification.  All four titles are from Elsevier.

Photochemistry & Photobiology (4 papers) and two journals of organic chemistry that have long shown a strong interest in isolating “natural products” from biological specimens are also represented. These are Tetrahedron Letters (3 papers) and its parent journal for longer papers and reviews , Tetrahedron. All are Elsevier titles.

In something of a break from that publisher, but staying consistent with his subject matter are Wiley’s Journal of Bioluminescence & Chemiluminescence (4 papers) and Luminescence ( 1 paper).  Wiley is also now the publisher of the title that contains Shimomura’s most quoted (2,904 citations) paper, which appeared in the journal now known as the Journal of Cellular Physiology (9 papers).

Shimomura might well have been less surprised at winning the chemistry award, if he perhaps reflected on the fact that he has appeared in two of the American Chemical Society’s leaders, the Journal of the American Chemical Society (2 papers), and Biochemistry (1 paper),  to say nothing of the papers in three of Japan’s important chemistry journals, Bulletin of the Chemical Society of Japan (1 paper), Chemistry Letters (2 papers), Bioscience, Biotechnology & Biochemsitry (1 paper), as well as the British Royal Society of Chemistry’s Chemical Communications ( 1 paper).

Shimomura has appeared in miscellaneous journals of biology, notably his home institution’s marine biology inclined Biological Bulletin ( 3 papers), the widely-read BioScience (1 overview paper) and Biophysical Journal (1 paper).

And as with most Nobel laureates, he has a track record of publishing in the usual prestigious multiscience journals, the Proceedings of the National Academy of Sciences (8 papers), Science (2 papers)  and Nature (2 papers). Not surprisingly for the cosmopolitan Shimomura, he adds the French leader, the Comptes Rendus de l’Academie  des Sciences, as well.

Martin Chalfie

Martin Chalfie is someone like Ramon y Cajal in that he has shown a special interest in the  nervous system, more specifically in the genetic control of its development, and someone like Camillo Golgi in that he does so by trying to understand what happens at the level of the cell.

While his most frequent publications of late have been in the usual multiscience leaders (Nature – 12 papers, Science – 6 papers, Proceedings of the National Academy of Sciences – 5 papers), a sampling of his other papers clearly bears this out.

The genetics/ development/ nervous system angle is demonstrated by the following.

·        There are 4 papers in Neuron (Elsevier’s Cell Press), 3 papers in the Journal of Neuroscience (Society for Neuroscience) ,  3 papers in Trends in Neurosciences (Elsevier) , and one paper each in the Journal of Neurochemistry (Wiley),  the Journal of Neurobiology (Elsevier), Nature Neuroscience (Nature Publishing Group), and Progress in Brain Research (Elsevier).

·        There are 3 papers in Genes & Development (Cold Spring Harbor Press), 3 papers in Development (UK’s not-for-profit Company of Biologists) , 2 papers in Genetics (Genetics Society of America, and single papers in the Annual Review of Genetics (the not-for-profit Annual Reviews, Inc.), Developmental Biology (Elsevier for the Society for Developmental Biology) Genome Biology (BioMed Central, the UK Open-Access publisher).

Chalfie’s  cellular bona fides   are attested to by:

·        Five papers in the Journal of Cell Biology (Rockefeller University Press), 3 papers in Cell (Elsevier’s Cell Press), 2 papers in the Journal of Cell Science (the UK’s not-for-profit Company of Biologists), and single papers in Cell Motility and the Cytoskeleton (Wiley), the Journal of Cellular Biochemistry (Wiley), Molecular Biology of the Cell (American Society for Cell Biology), and Molecular Cell (Elsevier’s Cell Press).

In many respects, his  4 publications in Current Biology, a nominally general biology journal, albeit one with a penchant for molecular and cellular biology (it’s from Elsevier’s Cell Press after all),  also attest to his strengths.

Roger Tsien

Not surprisingly many of Tsien’s papers appear in the same journals as do Chalfie’s and Shimomura’s. In fact, with over 300 articles, it’s very likely that he has published in every one of their journals at least once, and usually several times.

But his pattern is distinctive in a number of ways.

While he has more papers in the Proceedings of the National Academy of Sciences than anyone else in this group(32), he is in many ways the poster boy for the Nature Publishing Group, in much the same way that Shimomura seemed to be the best walking advertisement for publishing with Elsevier.

Consider that he has had 23 papers in the promethean Nature, as well 4 papers each in Nature Biotechnology,  and in Nature Methods; 3 papers each in Nature Cell Biology, and in Nature Reviews Molecular Cell Biology;   2 papers in Nature Protocols, as well as single papers in Nature Chemical Biology, Nature Genetics,. and Nature Neuroscience.

This is by no mean his only unique trait. 

Unlike Shimomura, he is very often (22 papers) an author in the Journal of Biological Chemistry. This is exceeded only by his 24 papers in Biophysical Journal from the Biophysical Society.

Tsien has a passion for review writing, and seems on track to set a record for publishing in different editions of the Annual Reviews, Inc. series. He has a paper each in the Annual Reviews of…..Biochemistry; Biophysics & Bioengineering; Cell  Biology, Neuroscience, and lastly Physiology.

Unlike both of our other Nobel authors he puts the “Physiology” into the Nobel Prize in Medicine or Physiology (once again, that’s the Nobel they did not get), for he has quite the track record in leading journals of that field, most notably, the British leader, from the Physiological Society, the Journal of Physiology – London (8 papers) as well as the US leader, the Journal of General Physiology (Rockefeller University Press for the Society for General Physiology), as well as the French society leader Journal of Physiology - Paris ( a review journal published by Elsevier), and even Acta Physiologica et Pharmacologica LatinoAmericana from Argentina.

But in many ways, his hallmark may well be his methods papers in a variety of venues, including within several of the Nature series, and of course, a paper that brings us full circle by appearing in the leading contemporary journal for that historic field that began this discussion, the Journal of Histochemistry & Cytochemistry (Histochemical Society, US).

Tony Stankus [email protected] Life Sciences Librarian & Professor

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

The 2008 Nobel Prizes in Medicine: In a Great Year for Virology in Particular, Would You Have Had The Journals They Needed?

The choices for recipients of the 2008 Nobel Prizes in Medicine or Physiology are among the most universally acclaimed as being judiciously decided, directly important to human health, richly  deserved, and if anything else worth noting, long overdue.

The focus this year was clearly on viruses directly linked to illnesses that affect millions of people.

A team of Parisians, Francoise Barre-Sinoussi  of the Pasteur Institute (France’s equivalent of the NIH) and Luc Montagnier (formerly of the Pasteur Institut and currently of the World Foundation for AIDS Research and Prevention, also in Paris) won for the discovery of the human immunodeficiency virus.

Harald zur Hausen of the German Cancer Research Center won for his discovery of the human papilloma viruses causing cervical cancer.

As is the custom with this blog and the Nobel Laureates, we will analyze the journals within which they published and ask ourselves if we, as information professionals, would have been able to be supply their needs from our own library’s resources.

This year we are using the Web of Science to compile this snapshot analysis, but would expect similar results in terms of percentages of papers in given categories of biomedical journals with PubMed, Biological Abstracts, Scopus ,  Excerpta Medica, and other databases that include a substantial representation of biomedical research journals.

Any differences would be largely owing to the number of journals covered, and in the depth to which individual authors in papers with very long strings of authors remain credited with given papers. (Some databases drop off authors after a given number. )

Francoise Barre-Sinoussi

Francoise Barre-Sinoussi has published most often (18 papers)  in The Lancet, but otherwise does not appear primarily in the leading journals of general clinical investigation.

She has had 3 papers in the Bulletin de l’Academie Nationale de Medicine, 2 papers each  in the Annals of Internal Medicine, and  the New England Journal of Medicine, and single papers in the American Journal of Medicine, JAMA, and the Journal of Clinical Investigation, plus a scattering of single papers in other less well known journals of this type.

Her clearest emphasis has been on journals of virology and retroviruses. 

She has 17 papers in AIDS Research & Human Retroviruses, and 10 papers in the journal now published as Microbes & Infection ( but formerly variously known as Annales de L’Institut Pasteur – Virology , Annales de Virologie , and Research in Virology).

She has 6 papers in Virology, 5 papers in AIDS,  and 4 papers in the Journal of Virology. 

Barre-Sinoussi   has 2 in the Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology.  She has single but highly characteristic articles in Acta Virologica, AIDS Research, Journal of General Virology, Journal of Virological Methods, and in Progress in Medical Virology.

Not too surprisingly her next most characteristic category of outlets are journals in general microbiology, immunology, and infectious diseases:  all of which routinely include papers on virology. 

She has 3 papers each in the Journal of Immunology, the Journal of Infectious Diseases, and Lymphology.

She has a single paper each in the American Journal of Epidemiology, Clinical and Experimental Immunology, Diagnostic & Clinical Immunology, FEMS Immunology & Medical Microbiology, Journal of Interferon Research, Medecine et Maladies Infectieuses, and finally Veterinary Microbiology.

While there are 47 other journals within which she has also published, we focus last on the major multiscience journals. They  figure into the CVs of virtually all Nobel Laureates in Medicine, and Barre-Sinoussi  is no exception.

She has had at least 9 papers in Science including her most cited (4,390 citations),  7 papers in Nature including her second most cited ( 2014 citations) as well as three papers in the Proceedings of the National Academy of Sciences, which while respectably cited, are not in the same citation earning league in her case.  

Her two papers in Cell   are by contrast, particularly heavily cited   (516 and 416 citations, respectively).

This is once again confirmation that Cell has become as much of a king-making journal as any of the major multi-science journals or major journals of general clinical investigation.

Luc Montagnier

Not too surprisingly, given that he co-authored a number of papers with Barre-Sinoussi, The Lancet was also the most frequent outlet for the work of Luc Montagnier (29 papers).

He has had at least double her number of papers in other journals of this type, including 6  in the New England Journal of Medcine, 5 in Presse Medicale ,  and 3 respectively, in the Annals of Internal Medicine, and the Journal of Experimental Medicine (arguably the general clinical investigation title with the strongest emphasis on immunology).

There were also notable single papers in JAMA and Nature Medicine .

Montagnier also has a strong concentration of papers in journals of virology and retroviruses.

AIDS Research & Human Retroviruses leads the pack with 23 papers, tied with the journal now known as Microbes & Infection, (formed by the merger of three journals of virology as noted earlier).

These are followed by  the Journal of Virology with 13, Virology with 11, and AIDS with 10.

The Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology comes next with 5 papers.

Intervirology and the Journal of General Virology have four papers each.

The Journal of Virological Methods has two papers.

Other journals with a strong component of virology, such as those in general microbiology, infectious diseases, and immunology are quite prominent.

Infection & Immunity has 7 papers, while the Journal of Infectious Diseases has 6.

Journals with two papers each include the European Journal of Immunology, Immunobiology, Immunology Today, the Journal of Immunology, Molecular Immunology and Vaccine.

Among the 104 other journals   featuring a single papers, the essays in the Annual Review of Immunology and the Annual Review of Microbiology are arguably the most important.

Montagnier has somewhat more papers (55) in the multiscience journals than does Barre-Sinoussi, but a good number of these are in fact co-authored with her.

His most famous papers in Science (4390 citations), Nature (2014), and Cell (516 and 416) were joint efforts with her.

This was also the case with an important methods paper in Virology ( 1255 citations.)

What distinguishes Montagnier from Barre-Sinoussi  most  is perhaps a greater interest in viruses and cancer, with Montagnier having 10 papers  in the Bulletin du Cancer and , 4 in the International Journal of Cancer. 

This observation forms a perfect bridge to the work of a man who has built his career on proving this causative connection in a manner that has already resulted in a preventive vaccine.

Harald zur Hausen

Today over 30,000,000 teenage girls are being greatly, if not yet perfectly, protected against cervical cancer by vaccines which set the body’s immune defenses on alert against an assortment of human papilloma viruses, which are now known to be the primary cause of this disease.

This progress is due largely to the dogged determination of Harald zur Hausen of the German Cancer Research Center in Heidelberg.

One reason for the difficulty that zur Hausen had in convincing his colleagues that microbes such as viruses could cause cancer lies in the fact that in 1926, a Danish researcher, Johannes Andreas Grib Fibiger was awarded the Nobel Prize in Medicine for announcing (in good faith, but with evidence that would be later overturned by new advances) that a microorganism that he termed, Spiroptera carcinoma, caused cancer. 

Since no fraud whatsoever was suspected of Fibiger, he got to retain his medal and the money, but the Nobel committee was clearly wary of awarding a second mistaken Nobel Prize  on a similar germ-cancer connection claim.

The 8,653 citation to zur Hausen’s articles apparently changed their minds.

Zur Hausen’s favorite outlets clearly display the dual themes of viruses and cancer that made up his life’s work.

He has 20 papers in Virology, 16 in the title now known as the International Journal  of Medical Microbiology (formerly the Zentralblatt ) , and 12 in the Journal of Virology.

The oncology side is represented most prominently by the  International Journal of Cancer (15 ), Cancer Research (7) and the Journal of the National Cancer Institute (3).

Despite the importance of his findings to everyday medicine, zur Hausen has not often appeared in the major journals of general clinical investigation. The Muchener Medizinische Wochemschrift and Deutsche Medizinische Wochenschrift are certainly respectable, but not of as great an impact as their English language competitors.

Zur Hausen’s greatest hits, however, are all written in English, and in a change from his fellow laureates this year, his two most cited papers  come from the Proceedings of the National Academy of Sciences (1440 & 744 citations, respectively.

Then comes Nature (in third place with 688 citations) and Science (in 5^th place with 485).

Fourth place is highly instructive. A reviews section of the pioneering post-WWII  multinational journal in biochemistry, Biochimica et Biophysica Acta (v.1288 no.2, :pgs.f55-f78) garnered 668 citations.

In many ways, it was the most expansive expression of his principal theory:  "Papillomavirus infections: A major cause of human cancers.”

Like Montagnier, he also published a major survey of his specialty in the Annual Review of Microbiology.

It is perhaps indicative of zur Hausen’s need to present his case systematically, over and over again, to a skeptical audience, that his dossier contain arguably the highest proportion of survey and tutorial papers of any of this year’s laureates.

One of every seven of his articles are major reviews.

Not only are some of the journals previously mentioned venues  for these expositions, but so are these:   Advances in Cancer Research, BioEssays,  the Cold Spring Harbor Symposia on Quantitative Biology,  Current Topics in Microbiology & Immunology, European Journal of Cancer, Interdisciplinary Science Reviews, Nature Reviews Cancer, Oncogene, and Seminars in Cancer Biology.

A Tribute to the Librarians Behind the Laureates

I am about 4 journals short of having everything cited here, a result that is admittedly made easier by the electronic access sharing of my flagship Fayetteville campus of the University of Arkansas , with the University of Arkansas for Medical Sciences library in Little Rock, some 150 miles away.

That kind of cooperation is made largely possible by administrators above my pay grade signing agreements with publishers and vendors on behalf of each institution’s faculty and students.

Good as that oversight is, we must give even greater honor to the librarians in France and Germany in the pre-electronic age when the careers of these Nobel Prizewinners kicked into high gear.

Those librarians somehow managed to acquire, organize, and facilitate the use of print resources for these scientists, particularly the journals which have always consumed the lion’s share of any biomedical library’s   budget.

So on behalf of all the people with AIDS, or those lucky enough to have avoided it, and for all the women who will not now get cervical cancer, and in memory of all who died of  it, we thank the librarians behind the laureates.

You made part of this progress possible. You make us proud to be librarians.

Tony Stankus [email protected] Life Sciences Librarian & Professor

University of Arkans Libraries MULN 233 E

365 North McIlroy Avenue

Fayetteville, AR 72701-4002

Voice; 479-409-0021

Fax: 479-575-4592

Marion vs. Melamine: A Timely New Book by Professor Nestle of NYU That Spotlights Pet Food Contamination As An Early Warning Sign of Ongoing Problems in Human Food Adulteration

It is entirely  appropriate that Marion Nestle, author of a key book on melamine contamination in pet food, holds an endowed chair in Nutrition, Food Studies, and Public Health at NYU, that is named after the late movie star Paullette Goddard.

In her just released work,  Pet Food Politics: The Chihuahua in the Coal Mine Nestle tells a story that is guiltily entertaining in much  the same way a Law & Order episode is: You know a crime has been committed, you just don’t know how, by whom, or for what reason.

The book is singularly instructive for a world that is naively shocked (but really should not be) that an adulterant deliberately mixed into  milk and baby formula, has in the past year, sickened at least 53,000 children in China (Barboza, 2008). 

She argues convincingly that regulatory authorities should have seen this sort of thing coming, because corrupt Chinese manufacturers had been doing exactly this sort of thing with pet food the year before, a scandal that eventually caused the largest product recall ever in that industry.

Her investigation disclosed that 42 brands of cat food and 53 brands of dog food were contaminated with melamine and a related compound cyanuric acid, that is often created through the breakdown of the melamine. (An important point:  Over time, if your feedstock  has melamine, you are likely also to have cyanuric acid present as well.)

A time line in this book, (pages 33-41),  discloses cases where sometimes a suspicious rice protein concentrate, or corn gluten, but much more often wheat gluten, were artificially “bulked up” in apparent (but not real) protein content through the deliberate mixing in of these nitrogen-rich compounds. (Traditional tests of protein content tend to measure the nitrogen level as a proxy for the protein content.)

Further, it disclosed that an increasing rate of dogs and cats were dying after eating pet food, but a direct causative link to a particular brand was complicated by the fact that one pet-food manufacturer actually makes the majority of pet food sold in this country, but then labels it with everything from a discount brand name to that of a super-premium variety. This is a fact not well appreciated by owners (or necessarily veterinarians at first).

To their credit, some of the pet food companies began palatability testing, only to find that their own test dogs and cats were getting sick, some to the point of needing to be euthanized.

In congressional testimony, one company executive lamely tried to explain this away by saying that the animals were kind of old anyway.

Early suspicions zero in on melamine contamination of the above mentioned grain protein concentrates, but this is complicated by the fact that some animals (including sheep) do not get sick, and that melamine had been historically fed to them with no ill effects.

Nonetheless, the Chief Financial Officer of the company that does the generic food manufacturing for these many brands coincidentally sold nearly half his shares in the company fairly early in this unfolding story.

Furthermore, when defective plant protein concentrates were rejected for pet food, they seemed to have somehow found    their way into chicken, hog, and aquacultured  fish feed, for animals intended for human consumption.

Necropsies of cats and dogs, carried out by a now alerted veterinary profession, repeatedly disclose mixed solid deposits of melamine and cyanuric acid crystals in the kidneys to the point where those organs malfunctioned enough to cause death. This combination deposit proved to be the culprit.

There were some entirely understandable mis-steps. Cornell University, called in with good faith to consult ,  by one company,  initially could not resolve the situation, although later, as part of a consortium of universities investigating they succeeded.

Testing methods for melamine were initially rather involved and expensive, but fortunately have now become   substantially simplified and cheaper.

While there is no lack of corporate indifference to the details of their operations and ingredients evidence by some company officials, there appears to have been truly clear cut criminality only on the part of a small, but apparently influential, number of Chinese manufacturers who deliberately sought to break into a cost-savings-at-all-costs pet food market by providing the cheapest possible ingredients, knowingly and completely misrepresenting their ingredients and purity  in a number of cases.

Furthermore, there seemed to have been a reluctance of Chinese officials to publicize or prosecute these criminals, because it would have made for bad publicity for the Olympics (at best) or, (at worst) quite possibly, because they did not want to alarm the rest of the Chinese public about yet another of a long chain of national food adulteration scandals in China.

What Nestle ultimately argues is that since food ingredients are bought from all over the world (apparently with a terrible lack of record keeping about who is the actual manufacturer) , with ingredient decisions based largely on cheapest price as opposed to best established reputation for quality, and the subsequent processing is concentrated in only a handful of US corporations, the chances for the mistaken approval by one company for a food product has great potential to affect many people at once, and to be very hard to trace in terms of the ultimate manufacturer of the tainted ingredient.

The only reliable answer to the quest for that company would be: “ It must have been that company we never heard of who sold it to us for prices that so low we couldn’t believe our ears.”

Politics, particularly corporate lobbying of government agencies and officials, is inevitably involved in food safety, often detrimentally, a theme for which Nestle is  famous.

Furthermore, the FDA is surprisingly powerless in many situations. Its realm of authority is not as great as many would imagine.

Attempts to warn or punish the Chinese food industry for absent or corrupt food protection practices seems to follow a sad formula: 

First they deny that any exist.

Then they identify a handful of particularly blatant perpetrators who are shot as an example.

And then they threaten to retaliate against American companies who dare blacken the names of Chinese companies by barring sales of American products  in China, a serious situation since China already has a vast trade surplus in dealing with the US.

But Americans should not be smug, and assume an air of innate national moral superiority, imagining that American would never do this to our own people or even to foreign customers. 

As reported in an exceptionally insightful Op-Ed piece in the September 30^th, 2008, New York Times by Bee Wilson (see below), the US has a very similar history when it comes to milk contamination in an effort to stretch supplies, lower the costs to dairy bottlers, and disguise the foul, watered-down, and tainted swill corrupt corporations back then passed onto New York City consumers.

In 1853 it was discovered that the total honest output of the Westchester and Orange county dairies   that made up almost the entire milk supply for the New York City market, was no more than 90,000 quarts a day, but that somehow dairy bottlers managed to sell 120,000 a day, with the difference being made up just the 1800’s versions of the adulterants used in the 21^st century.

Up to 8,000 American children were dying every year in that city, and it took decades to clean up.

In any case, the evidence today suggests that BioMedical Librarians should not ignore recent history, such as that reported by Marion Nestle,  in attempting to assist current clinicians trying to resolve the mysterious food-borne illnesses of consumers today.

Andersen WC  et al. 2008. Determination and confirmation of melamine residues in catfish, trout, tilapia, salmon, and shrimp by  liquid chromatography with tandem mass spectrometry. Journal of Agricultural and Food Chemistry 56 (12): 4340-4347.

Barboza D. 2008. China detains 22 in tainted-milk case. The New York Times (September 30, 2008. Internation. P.A11.

Burns K. Researchers examine contaminants in food, deaths of pets.  Journal of the American Veterinary Medical Association 231 ((11): 1636-1638.

Buur JL,  Baynes RE & Riviere JE. 2008. Estimating meat withdrawal times in pigs exposed to melamine contaminated feed using a physiologically based pharmacokinetic model.  Regulatory Toxicology and Pharmacology 51 (3): 324-331.

Cianciolo RE et al.  2008. Clinicopathological, histologic, and toxicologic findings in 70 cats inadvertently exposed to pet food with melanine and cyanuric acid. Journal of the American Veterinary Medical Association 233 (5): 729-737.

Dobson RL  et al. 2008. Identification and characterization of  toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs.  Toxicological Science  epub  ahead of print.

Filgenzi MS et al.  2008. Diagnostic determination of melamine and related compounds in kidney tissue by liquid chromatography/tandem mass spectrometry.  Journal of Agricultural and Food Chemistry 56 (17): 7593-7599.

Garber EA. 2008. Detection of melamine using commercial enzyme-linked immunosorbent assay technology.  Journal of Food Protection 71 (3): 590-594.

Haller C.  2008. Made in China. Journal of Medical Toxicology 4 (2): 141-142.

Nestle M. 2007.  Food Politics: How the Food Industry Influences Nutrition and Health. Berkeley, CA: University of California Press. (revised & updated, originally published in 2002)

Nestle M. 2004. Safe Food: Bacteria, Biotechnology, and Bioterrorism.  Berekeley, CA: University of California Press.

Nestle M. 2007. What to Eat. NY: North Point Press.

Nestle M & Dixon, LB eds. Taking Sides: Clashing Views on Controversial Issues in Nutrition and Food. NY: McGraw-Hill.

Nestle M & Nesheim MC. 2007. Additional information on melamine in pet food. Journal of the American Veterinary Medical Association  231 (11): 1647.

Parry J. 2008. China’s tainted infant formula sickens nearly 13,000 babies. BMJ 3337: 1802.

Wilson B. 2008. The swill is gone. The New York Times (September 30, 2008. Op-Ed, p.A31.

Tony Stankus [email protected] Life Science Librarian & Professor

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

Gastric Lap-Band Weight-Loss Surgery vs. Gastric Bypass Weight-Loss Surgery vs. a Rigorous, Medically Supervised Diet, Prescription Medicine, and Exercise Program for Long Term Weight Loss in the Chronically & Severely Adult Obese

Weight loss surgery is becoming vastly more common, and the number of cases is well over a quarter of a million annually worldwide, with about 200,000 in the US alone. 

Great as these figures are, the number of these surgeries almost doubles each year.

The number of hospitals in the US   where they are performed is probably about 400, although the number of them that qualify as “Centers of Excellence,” is currently 351.

The closest thing that this still new surgical specialty has to a certification board is the American Society for Metabolic and Bariatric Surgery, which has 607 surgeons it considers particularly qualified to do these procedures.

This patient-to-surgeries ratio would be worrisome, excepting for the universally recognized fact that the best results seem to come from surgeons who do a lot of these procedures in places where a lot of these procedures get done. 

It is a kind of circular logic, but it actually proves true in this case.

The only thing growing faster it seems, are the number of television ads for adjustable lap band weight-loss surgery.

Adjustable lap band weight-loss is trying to make up lost ground since it was approved for wider use by the FDA  (which has the power to regulate surgical devices in addition to drugs) about 5 years after Roux-en-Y gastric bypass surgery took off.

Both procedures   (and several less-used variants) have flourished with the advent of minimally-invasive approaches. Consequently,   acronyms like  Laparoscopic Roux-en-Y gastric bypass (LRYGB)  and Laparoscopic Adjustable Gastric Banding  (LAGB) are becoming quite a bit more common in memos from surgeons and nurses to their biomedical librarians.

How do these two competing surgical procedures compare to a rigorous, medically supervised regimen  of dieting, exercise, and weight-loss prescriptions for the long term maintenance of weight loss in the chronically obese?

And of the two most commonly performed surgical approaches, which is better?

What does the evidence say?

An important article (O’Brien et al, 2006) in the Annals of Internal Medicine, scarcely a vehicle for promoting surgery of any type when non-surgical medical interventions might do as well,  admitted quite bluntly that the treatment of mild to moderate obesity with LAGB  was significantly, statistically superior to an intensive medical program of dieting, multiple visits to the internist’s  office, psychotherapy,  and weight-loss drug prescriptions (Orlistat™). 

This does not mean that the dieting/exercise/prescriptions school of thought   has abandoned continuing research.

ClinicalTrials.gov  reports 159 ongoing studies on weight loss, with a preponderance dealing with some combination of medical supervision, restricted eating , exercise and overall behavioral modification,  most with the hope, but rarely proven  result, of  sustaining that weight loss over several years in the majority of their human subjects.

But there still remain some serious unanswered questions (see Frank, 2006).

For the time being, the evidence for long term maintenance of weight loss favors surgery over attempts at remaking human nature and physiology for the vast majority of chronically obese individuals.

Both of the most common laparoscopic procedures have valid claims to advantages relative to each other, supported by some of the literature.

It is fairly clear, for example, that the LAGB procedure is less drastic and is more readily reversible, in the sense that the surgical band is made to be loosened or tightened fairly easily.

Hospital stays with LAGB are generally quite short and a 24 hour cycling through is not unusual.

And, up until 2006, based largely on European and Australian case histories (since the procedure was used earlier and more widely there) LAGB appeared to better for the super obese; those with BMI over 60.

But a 2006 article  by Bowne et al. reported that LAGB patients had more late complications, reoperations, less weight loss and decreased overall satisfaction when compared to a match group having a LRYGB.

Of particular note was that some patients had as many as 15 “adjustments” in order to attain the right size of stomach for them to have consistent weight loss. However, most of these can be done on an office visit or day surgery basis.

This is not to say that LRYNGB   patients were without mishaps or complications. In fact, these occurred earlier in the post operative period, and contributed to adding up to 3-5 days to the typical hospitalization.

Up until this very month, the only clear-cut advantage that every study agreed upon was that LRYGB procedures resulted in more weight loss, and intriguingly seemed to have much better results for patients with adult onset (Type II) diabetes much more often, although the causal mechanism was not well   understood.

But a spate of studies and reviews (e.g. Bult et al. 2008, Holdstock et al., 2008, and most notably a lab animal study, Troy et al. , 2008, in the prestigious journal Cell Metabolism) have suggested that the reason for this weight loss with diabetes resolution is very likely to be  that LRYGB fundamentally changes, in a decisive and quite favorable way, the hormonal and regulatory peptide flux that involves weight-related  substances like ghrelin and glucagon-like peptide-1.

Perhaps an even bigger surprise than the study in Cell Metabolism was a report this month (September, 2008) in the American Journal of Managed Care (Cremieux et al. 2008). 

The Analysis Group, an economic, financial, and strategy planning consulting firm in Boston reported that, while they admittedly could not know all the variables in advance and suggested prospective trials to test their hypotheses,  their calculations suggested that the $17,000-$26,000 paid out per person on average, for bariatric surgery by insurance companies, seemed quite likely to pay for itself in reduced medical claims after two years for the more frequently encountered case of laparoscopic weight-loss surgeries, and after four years for the less common case “open” weight-loss surgeries.

If this projection holds up, expect more demand for searches and information on bariatric   surgery.

Neither this country, nor the world in general, is running out of obese adults who could very likely benefit from it.

Angrisani L, Lorenzo M & Borrelli  V. 2007. Laparoscopic adjustable gastric banding versus Roux-en-Y   gastric bypass: Five year results of a prospective randomized trial. Surgery for Obesity and Related Diseases 3 (2): 127-132.

Batsis J et al. 2008. Cardiovascular risk after bariatric surgery for obesity. American Journal of Cardiology 102 (7): 930-937.

Bult MJF, van Dalen T, Muller AF. 2008. Surgical treatment of obesity. European Journal of Endocrinology 158: 135-145.

Bowne WB et al. 2006. Laparoscopic gastric bypass is superior to adjustable gastric band in super morbidly obese patients: A prospective comparative analysis. Archives of Surgery 141 (7): 683-689.

Buchwald H. 2008. Introduction and current status of bariatric procedures. Surgery for Obesity and Related Diseases 4 (Supplement 3): s1-s6.

Champion JK & Pories WJ. 2005. Centers of excellence for bariatric surgery. Surgery for Obesity and Related Diseases 1 (2): 148-151.

Cheng AKS & Poon L. 2007. A comparison of four different proprietary gastric bands. ANZ Journal of Surgery 77 (May Supplement): 46-47.

Cremieux PY et al. A study on the economic impact of bariatric surgery. American Journal of Managed Care 14 (9): 589-596.

Engstrom BE et al. 2007. Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery.  International Journal of Obesity 31 (3): 476-480.

Fielding GA. 2003. Laparoscopic adjustable gastric banding for massive superobesity (> 60 BMI). Surgical Endoscopy 17 (10): 541-1545.

Frank A. 2006. Bariatric surgery: Too many unanswered questions. American Family Physician 73: 1403-1408.

Holdstock C et al. 2003. Ghrelin and adipose tissue regulatory peptides: Effect of gastric bypass surgery in obese humans. Journal of Clinical Endocrinology and Metabolism 88 (7): 2999-3002.

Holdstock C et al. 2008. Postprandial changes in gut regulatory peptides in gastric bypass patients. International Journal of Obesity  epub ahead of print.  doi: 10.1038/ijo.2008.157.

Jan JC et al. 2007. Comparative study between laparoscopic adjustable gastric banding and laparoscopic gastric bypass: Single-institution, 5-year experience in bariatric surgery. Surgery for Obesity and Related Diseases 3 (1): 42-50, follow up discussion 50-51.

Korner J et al. 2006. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity 14 (9): 1553-1561.

Lancaster RT   & Hutter MM. 2008. Bands and bypasses: Thirty-day morbidity and mortality of bariatric surgery as assessed by prospective, multi-center, risk-adjusted ACS-NSQIP data. Surgical Endoscopy epub ahead of print.

Lyass S et al. 2005. Device-related reoperations after laparoscopic adjustable gastric banding. American Surgeon 71 (9): 738-743.

Muller MK et al. High secondary failure rate of rebanding after failed gastric banding. Surgical Endoscopy 22 (2): 448-453.

Nguyen NT  et al. 2005. Accelerated   growth of   bariatric surgery with the introduction   of minimally  invasive   surgery.  Archives of Surgery 140 (12): 1198-1202.

O’Brien PE   et al.  2006.  Treatment   of mild to moderate obesity with laparoscopic adjustable banding   or an intensive   medical program. Annals  of Internal Medicine    144: 625-633.

Rendom SE & Pories WJ. 2005. Quality assurance in bariatric surgery. Surgical Clinics of North America 85: 757-771.

Tan KY, Rao A. & Ramalingam G. 2007. A comparison    of four  different proprietary gastric bands.  ANZ Journal of Surgery 77 (May Supplement): 46-47.

Troy S et al.  2008. Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice. Cell Metabolism 8: 201-211.

Tony Stankus [email protected] Life Sciences Librarian & Professor

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

Is Transgenic Introgression Automatically Transgression? Do Genetically Modified Crops Threaten Wild Species (or Ourselves) With Extinction?

Introgression is the process by which one species, usually a plant (although animal models clearly exist), hybridizes with another. Then, the resulting second generation mixed species then hybridizes again with one or the other of the initial parent plants.  If that second generation hybrid is itself able to reproduce and thrive, its existence is said to represent a stable introgression.

Linnaeus , the great classifier of plants and animals, won a prize from the St. Petersburg Academy of Sciences in Russia in the 1700’s when he successfully hybridized two related but nonetheless distinct plants.  The point he was trying to prove at that time was that plants can reproduce sexually (which of course, many or most can), but he also suggested that this hybridization in nature might well be the source of many (or even most ) new species.

Linnaeus was right up to a point.  But as orchid and rose breeders  will tell you, the creation of new hybrids, to say nothing of new species, rarely goes as easily or as planned as that.

A great many hybrids are sterile, that is, they cannot reproduce, even if they can thrive for a single generation.

Other hybrids unravel in terms of their hybrid appearance or in terms of their desirable properties and go right back to being more like their native ancestors. (They revert to being wild.)

A fairly common occurrence among hybrids appears to be that they have seeds that are too small for successful soil penetration, or which will sprout only in well-tilled soil and only under gentle conditions.

Other hybrids are unable to compete with either parent plant once they sprout, and simply go out of existence themselves.

All these points about introgression in plants would be almost purely academic save for a new worry: the effect of genetically modified (hereafter, GM) crops and their nearby wild plant relatives, and both human and wild creature life. 

The most commonly encountered GM crops are soybeans, cotton, corn, canola (rapeseed oil), squash, alfalfa, rice and now, potatoes.

The most common traits which are introduced by GM are increased resistance to harmful insects, decreased susceptibility to weed killers (i.e. enabling weed killers to be used without harming the main crop), the ability to thrive or utilize better what water and fertilizer is available so as to increase yield, and in food crops , the ability to synthesize or maximize other missing or low levels of nutrients for humans.

Will their GM genes introgress into the native species and somehow wipe them out?

Or will there be other and more insidious unintended consequences than can only be imagined at this time.

Current opinion on GM introgression is more politically driven, than experience based, and therefore working assumptions are unsurprisingly diametrically opposed.

A recent  editorial in the June 2, 2008 issue of America’s conservative flagship, The National Review , says that holding GM back retards the ability of Third World countries to feed themselves, and cites Robert Mugabe and Hugo Chavez, as prime examples of GM opponents who are consumed by conspiracy theories of GM, rather than by the existing science concerning GM crops.

But that journal’s  equally prestigious liberal American counterpart, The Nation, warns in its May 12, 2008 issue, that efforts by agribusiness to promote GM crops are deliberately designed to maximize profits, not solve the world food crisis. In fact, the journal suggests that getting poor farmers hooked on GM seeds will eventually impoverish them, and starve their families and produce customers.

The European Union on the whole agrees with the The Nation, and has either bans, or high regulatory barriers, on many GM foods including plants, that are driven by fears of what some commentators refer to as the unpredictable consequences of having Europeans eat “Frankenfood.”

But perhaps the most balanced scientific assessment, and one that merits wider distribution among politicians is found in the May 2008 issue of BioScience (v.58, no.5, p.379). Its essential message is:

"So far, careful scrutiny has found no evidence of health dangers from growing or eating genetically engineered crops. Certainly any ecological or health consequences of these products need to be monitored and prudence observed.”

Have there been unintended outbreaks of GM hybridization?

Yes.

The most common reasons reported for these outbreaks are planting GM crops too close to stands of non-GM or wild varieties so that there is pollen interchange,  and random dispersals of GM seed along truck routes through tire treads or through adherence of seed or pollen to workers clothing.

One example is the hybridization of one GM member of the turnip family (the oil-seed rape plant Brassica napa) with  Brassica olearacea or with Brassica rapa (two turnip top greens favoring varieties ) which thrive better in the wild.

In another case, a ten year study indicated that some GM sunflowers had in fact, hybridized with wild sunflowers.

In yet another, a GM variety of rice had indeed introgressed into a wild rice variety.

In still another, wild lettuce had co-mingled with GM lettuce.

Have those consequences been of any great significance?

No.

Sampling of the Brassica  indicated that at one point in 2002, 85 out of 200 plants sampled near the zone of hybridization, had in fact, shown some evidence of introgression, but by 2005 it had gone down to 5 out of 200.

The GM introgression yielded wild sunflowers that turned out to have greater hardiness, including the ability to withstand better harsher environmental conditions, particularly less water and poorer soil.

The rice study showed that even with close co-planting, the risk for transgenic hybridization was much less than 1%, and that the farther away from the experimental field, the risk diminished to a virtual zero point. Nearby wild grasses that had the theoretical capacity for introgression, were complete unaffected.

The lettuce collision showed that the wild type favoring hybrid was actually more likely to survive than the cultivated one , so the chance of the GM favoring hybrid running amuck seemed unlikely, because it was in fact, less viable outside its intended area of cultivation.

Probably the most serious wildlife consequences any of these hybridizations is alleged to have is on insects and insect eaters.

Butterflies and moths  dependent on one type of flower may not do as well on the GM introgressed hybrid variety.

Streamside plants that have hybridized with GM plants that are insect resistant, may support fewer insects to fall into in the water for fish to eat.

The environmental upsets that have been detected have not been documented as yet to be persistent. And the odds are they will not in fact be so.

There are some rare but somewhat more realistic worries about human health in that  genes for certain proteins -----most commonly mentioned are  nut proteins-----to which some people are allergic may unintentionally migrate through GM to a plant which was previously not known to cause this particular allergic reaction, so that the consumer was taken unaware. Certain soybeans have been found to contains proteins from brazil nuts, for example.

But conversely,  there is already progress on creating allergy medicines using transgenic rice, and vaccines have been made using transgenic potatoes.

In any case, the clearest recommendation about GM and introgression, and its benefits and risks, that can be drawn for biomedical librarians for now, is a very reliable one: Encourage your clientele to read  more of the science.

The very thought alone of GM crops should not make your readers fact-resistant.

Auer C. 2008. Ecological risk assessment and regulation for genetically-modified ornamental  plants. Critical Reviews in Plant Sciences 27 (4): 255-271.

Beardsley TM. 2008. The right fight for biologists. BioScience  58 (5): 379.

Chandler S & Dunwell JM. 2008. Gene flow, risk assessment and the environmental release of transgenic plants. Critical Reviews in Plant Sciences 27 (1): 25-49.

Choo V. 1996. Allergens can be transferred to transgenic products. The Lancet 347 (9004): 819.

Dlugosch KM  & Whitton J. 2008. Can we stop transgenes from talking a walk on the wild side? Molecular Ecology 17 (50; 1167-1169.

Ford CS et al. 2006. Spontaneous gene flow from rapeseed (Brassica napus) to wild  Brassica oleracea.  Proceedings of the Royal Society of London B – Biological Sciences 273 (1605): 3111-3115.

Hooftman DAP et al. 2005. Demographic vital rates determine the performance advantage of crop-wild hybrids in lettuce. Journal of Applied Ecology 42 (6): 1086-1095.

Hooftman DAP et al. 2008. Modelling the long term consequences of crop-wild relative hybridization: A case study using four generations of hybrids. Journal of Applied Ecology 44 (5): 1035-1045.

Hooftman DAP et al. 2008. Modelling the consequences of crop-wild relative gene flow: A sensitivity analysis of the effects of outcrossing rates and hybrid vigor breakdown  in Lactuca. Journal of Applied Ecology 45 (4): 1094-1103.

Liang GH & Skinner DZ.  2004. Genetically Modified Crops: Their Development, Uses, and Risks. Binghamton, NY: Food Products Press, a division of Haworth Press.

Ma S & Jevnikar AM. 2005. Transgenic rice for allergy immunotherapy. Proceedings of the National Academy of Sciences 102 (48):  17255-17256.

McNamee D. 1999. Transgenic potatoes produce oral HBV vaccine. The Lancet 354 (9191): 1707.

Mercer KL et al.  2007. Stress and domestication traits increase the relative fitness of crop-wild hybrids in sunflower. Ecology Letters 10 (5): 383-393.

Moeller L & Wang K. 2008. Engineeering with precision: Tools for the new generation of transgenic crops.

Nichols J. 2008. The world food crisis. The Nation (May 12^th  issue): p.6-7.

Rong J et al.  2005. Low frequency of transgene flow from Bt.Cp TI rice to its non transgenic counterparts planted at close spacing. New Phytologist 168 (3): 559-566.

Rosi-Marshall EJ et al. Toxins in transgenic crop byproducts may affect headwater stream ecosystems. Proceedings of the National Academy Of Sciences 104 (41): 15204-16208.

Schwarz F. 2008. Transgenic travesty. National Review  (June 2^nd issue): 20-21.

Singh O.V, Ghai S & Paul D. 2006. Applied Microbiology and Biotechnology 71: 598-607.

Stewart CN. 2004. Genetically Modified Planet: Environmental Impacts of Genetically Engineered Plants. New York: Oxford University Press.

Thomson JA. 2007. Seeds for the Future: The Impact of Genetically Modified Crops on the Environment. Ithaca, NY: Cornell University Press.

Vonder Leppe M & Kowarik I. 2007. Crop seed spillage along roads: A factor of uncertainty in the containment of GMO. Ecography 30 (4): 483-490.

Wang F et al. 2006. A large-scale field study of transgene flow from cultivated rice (Oryza sativa) to common wild rice (O. rufipogon) and barnyard grass (Echinochloa crusgalli).  Plant Biotechnology Journal 4 (6): 667-676.

Warwick  SI et al. 2008. Do escaped transgenes persist in nature? The case of an herbicide resistance transgene in a weedy Brassica rapa population. Molecular Ecology 17 (5): 1387-1395.

Wei W & Darmency H. 2008. Gene flow hampered by low seed size between oilseed rape and five wild varieties. Seed Science Research 18 (2): 115-123. 

Tony Stankus [email protected] Life Sciences Librarian & Professor

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

Are Conjugated Linoleic Acids the Next Omega-3 Fatty Acids? The Serious Promise and the Sometimes Over-the-Top Hype of an Over-the-Counter Supplement: CLA

In 1979 Dr. Michael Pariza of the University of Wisconsin was frying hamburger in his lab with the full intent of proving that ground beef or the process of frying hamburger at high heat would certainly yield cancer-causing compounds.

After all, did it not seem at that time, and this one too, that everything, sooner or later was going to be found to cause cancer?

He took the resulting meat juices and painted them on some nude-skin mice, which were typically used to detect carcinogenic activity. The mice did not get skin cancer nor any other kind of cancer.

He then painted a known cancer causing compound on the mice as well as the hamburger juices, figuring that the hamburger juices might potentiate or stimulate even more cancer-causing damage, even if they were not the prime movers.

  Instead of getting the predicted cancer worse, the mice did not get it at all.

This serendipitous finding, that a category of substances within these hamburgers, called Conjugated Linoleic Acids, possessed potent cancer-inhibitory processes, was soon published in the Proceedings of the American Association for Cancer Research, and began an incredible career for Dr. Pariza and his lab as not only researchers, but maintainers of a clearinghouse for information on these CLAs.

A search of the Web of Science done today (August 25, 2008) disclosed over 2100 articles on CLAs.

While no responsible researchers claim that CLAs are a cure-all for cancer or for a broad variety of ailments, there is a very large body of evidence that some of the isomers in the CLA family do possess fairly marked medicinal or metabolic properties.

What are they?

Weight loss and body fat reduction are two of the most common claims made for the intake of CLAs. While the results are inconsistent, the preponderance of evidence suggests that CLA intake does work in weight loss, particularly among those who are overweight and obese, but otherwise of good health.  There is even some evidence that they can forestall the Thanksgiving-Christmas-New-Year’s holiday weight gain that so many of us experience.

The most commonly proposed mechanism of action for the CLAs is to activate apoptosis, the programmed cell death, of fat cells.

There is much less evidence solidly favoring CLAs as a supplement to combat metabolic syndrome and insulin resistance, although one isomer seems fairly effective in reducing the girth fat that is an important part of this insidious condition.

Once again, the proposed mechanism of action is the promotion of fat cell apoptosis. Unfortunately, some isomers may actually worsen insulin sensitivity; i.e. increase insulin resistance.

Cancer data are promising but also mixed. Breast cancer reduction or avoidance, stomach and colon cancers, and prostate cancers all seem to respond well in the lab to treatments involving CLAs, but these are almost all non-clinical trials.

Cardiovascular health, atherosclerosis, and favorable lipid profiles sometimes result when experimental subjects are taking CLAs, but there are a minority where the opposite occurs.

The promise of these CLAs is such that 2006 sales, the most recent for which we have data, shows that $460 million was spent in over-the-counter supplements of CLAs, largely purchased in nature food stores and over the internet.

While there is little evidence that these CLA preparations are toxic to most people. They are not without their problems.

• First, the most common CLA isomers are cis-9, trans-11, and trans-10, cis-12, but several other types are encountered in nature in lesser amounts, and still others can be prepared in the lab.  So-called all-natural supplements , usually made from various seed oil preparations involving safflower, sunflower, or soybean, tend to vary  in the relative percentage of these ingredients from batch to batch, and from season to season, owing to the natural fluctuation of the isomers in the plant material sources. The consumer is often unaware that what he or she is taking is likely to vary in formulation, which ought to be an important consideration if one isomer does something better physiologically than another isomer.
• Second, there is a distinct possibility that some of these isomers, most commonly the trans-10, cis-12, has been reported as having adverse consequences, particularly in those who have adverse blood lipid profiles. This isomer’s benefits may well outweigh its risks for some patients, but without a firm grasp on which preparations have which concentrations at any given time, an informed judgment cannot be made.
• Third, it is very clear that CLAs often have fabulous curative or preventive results in lab rats. With humans, the picture is far less clear.

Nonetheless, there is absolutely no let up in clinical and animal trials. The people in the beef, dairy, sheep and even pork, poultry & egg businesses have been rapidly developing ways to feed their livestock in a manner that would naturally increase the levels of CLAs within customary proportions, so that one could get their dose as a part of a diet.

This would essentially turn a glass of milk or a hamburger into a kind of CLA nutraceutical. 

Don’t laugh, eggs have had a fairly dramatic rebound in sales over the last few years once it was found how a farmer might be able to increase naturally their levels of highly beneficial omega-3 fatty acids, perhaps even offsetting the now somewhat discredited egg-eating-cholesterol- raising dilemma. (Genetics raises cholesterol at least as much as eating eggs, in many, many patients. Eating a limited number of eggs per week is now seen as much less threatening than before, and eggs are frankly otherwise excellent nutritionally.)

Even now, there are numerous announcements of agricultural experimental station scientists being able to increase naturally through animal nutrition methods both CLAs and omega-3s at the same time, hoping perhaps to double their sales, as they improve the overall healthiness of their products.

For a longer review written especially for librarians, one with over a 100 references, see the article below by this blogger.

Cachaldora, P et al. 2008. Double enrichment of chicken eggs with conjugated linoleic acid and n-3 fatty acids through dietary fat supplementation. Animal Feed Science & Technology 144 (3-4): 315-326.

Plourde, M. et al. Conjugated linoleic acids: Why the discrepancy between animal and human studies? Nutrition Reviews 66 (7): 415-421.

Stankus, T. 2008. Turning meat, poultry, eggs, and dairy products into nutraceuticals through increasing their conjugated linoleic acid levels, Part one: Reviewing the literature of benefits claimed for conjugated linoleic acids in human health. Journal of Agricultural & Food Information 9 (3): 229-255.

Watras, AC et al. 2007. The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain. International Journal of Obesity 31 (3): 481-487.

Tony Stankus [email protected] Life Sciences Librarian & Professor

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

H5N1: Update on Avian-to-Avian & Avian-to-Human FluTransmission, Testing, Vaccines, Mortality Rates, Symptomatology, Hospitalization Rates

The years 2003-2004 saw outbreaks of what we now know as H5N1 Avian flu virus in eight East Asian countries: Cambodia, China, Indonesia,   Japan, Laos, South Korea, Thailand,  and Vietnam.  It has since spread to Egypt, India, Kazakhstan, Russia and the US, but at much, much lower rates, sometimes with only a few cases per country. This blog will update the reader with some of what has been newly learned, or more strongly confirmed, since then, without “The Pandemic Will Wipe Us Out Tomorrow” hype that has the potential for desensitizing a community that has grown skeptical that Avian flu is much of  a threat to anyone, when, in fact it is.

What Birds (“Avians”) Transmit the Virus That Causes the Disease?

Thus far it is pretty clear that two categories of poultry seem to be responsible for most of the outbreaks that spread to humans.

Domestic poultry, basically chickens and ducks grown for home consumption or the marketplace, seem to be the primary carriers from which most humans contract the disease.

These birds can get it from one another, or from migratory waterfowl.

Which Migratory Waterfowl Appear to Be The Culprits?

The family of birds called Anatidae, which consists of ducks, geese and swans are the most likely international vectors. Seagulls have been implicated, but not to as great a degree.

This bit of detective work has primarily used two pieces of evidence: Finding infected migratory birds and then tracking paths of infection along migratory flyways. The match up is good, although trucking of poultry infected by wildlife to cities that are not part of the migratory birds’ flyway can complicate the picture.

The means of transmission from migratory to domestic fowl seems to be through the migratory birds fouling the water and land with their often copious and virus-shedding feces.

The domestic fowl incorporate the viruses through contact or ingestion, and then pass it to on to other members of the domestic flocks through contact and their own virus-laden defecation.

One of the most imaginative studies of risk evaluation   from migratory birds comes from Australia, where scientists have co-mapped the locations of poultry farms and the breeding grounds of sea birds and water fowl, and found only a narrow overlap. This will allow them to focus better their preventive efforts.

What about other animals? Rats and pigs can be infected with the virus, but only in experimental settings, and seem not to be likely to become vectors.

Is H5N1 Everywhere Identical?

No, there are at least five different strains, (and a number of related viruses since discovered, like H5N2 ) most of which get named after the location from which they were first isolated, or from where the most cases were reported.

There has already been  some rate of mutation among these.

The good news is that most respond to the same drugs.

The bad news is that some of the newer strains appear more virulent.

How Can We Tell the Strains Apart?

Probably the most rapidly progressing area in the field is the differentially diagnostic molecular sequencing of these viruses. Tests are becoming more reliable, faster, more portable, and even cheaper.

False positives remain a problem, but by and large, that is better than false negatives, which would leave patients without any treatment.

What Are The Current Treatments?

By far, the most common treatment is with oseltamivir carboxylate, whose brand name is Tamiflu™. While it is not equally effective against all H5N1 strains, it has been able to be prepared in the multimillions of doses and to have some activity against virtually all of them.

The use of adjuvants (chemicals that seem to boost vaccine performance) and the timing of the injections seem to be more important to current successful treatment  than the lack of specificity to all strains at this time of vaccines like Tamiflu™, although the development of cheap, and quickly scalable production of  strain-specific vaccines or the development of multivalent vaccines that can inhibit the entire class of H5N1 are ultimately the long term goal.

Curiously, there is a good news/ bad news dichotomy with regard to the longer lasting nature of the drug in waterways. Apparently, it lasts up to two weeks in ponds and rivers. This might seem to suggest that treated humans who wash, void, or defecate nearby could actually decrease the water’s viral load. More likely, however, over-exposure of the drug could induce drug resistance as susceptible strains quickly fall prey, leaving only resistant mutants.

What Are Today’s Mortality Rates?

The most on-point study thus far is Kundun et al. below, from August 14^th, 2008 issue of  The Lancet . They reported 127 cases in Indonesia, occurring between June 2005 – February 2008.

The mortality was a whopping 81%.

What Are the Common Factors in Exposure to the Virus?

Living in an area where poultry had died with avian flu (30%)

Handling sick or dead poultry (21%)

Being around healthy poultry (15%)

Slaughtering or processing the meat of sick poultry (15%)

H5N1 positive poultry in the home or neighborhood, even if the poultry were apparently healthy at the time (5%).

Visited “wet” market where poultry was slaughtered at point of purchase. (3%)

Handled H5N1 positive poultry feces (perhaps as part of  an attempt to clean it out.) (1%)

Symptomatology

Fever (93% of patients), cough (32%), runny nose (17%), nausea/vomiting (7%-13%), vertigo (10%), diarrhea (7%0, headache (6%),  muscle aches (1%).

Rates of Admission to Hospital & Effectiveness of Treatment

125 patients were admitted to a hospital. One recovered with treatment at home; the other refused treatment and died. The sooner a patient was admitted to a hospital, the better were his or her chances. Likewise with the onset of treatment with Tamiflu™.

Nonetheless, most patients did die, typically of pneumonia.

The study suggests that the reason for the high death rate was that the hospital admission was too late after the onset  of the disease, likewise with the administration of the Tamiflu™. 

A curious result was the fact that patients who were part of a group that got ill, had better chances of recovery, than did patients who came down sick with the virus with no apparently sick  neighbors, co-workers or family members. This could be because public health workers or primary care physicians were less alert to the possibility that this patient’s cold or flu was in fact, H5N1 based, until   it was too late.

Bartels P & von Tumpling W. 2008. The environmental fate of the antiviral drug oseltamivir carboxylate in different waters. The Science Of The Total Environment epub ahead of print, no volume or pagination yet assigned. DOI: 10.1016/j.scitotenv.2008.06.032

Chantratita W, et al. 2008. Qualitative detection of avian influenza A (H5N1) viruses: A comparative evaluation of four real-time nucleic acid amplification methods. Molecular And Cellular Probes epub ahead of print, no volume or pagination yet assigned. DOI: 10.1016/j.mcp.2008.06.005

East IJ, Hamilton S & Garner G. 2008. Identifying areas of Australia at risk of H5N1 avian influenza infection from exposure to migratory birds: a spatial analysis. Geospatial Health 2 (2): 203-213.

Gaidet N, et al. 2008.Evidence of infection by H5N2 highly pathogenic avian influenza viruses in healthy wild waterfowl. PLoS Pathogens 4(8):e1000127.

Gilbert M, et al. 2006. Anatidae migration in the western Palearctic and spread of highly pathogenic avian influenza H5NI virus. Emerging Infectious Diseases 12 (11):1650-1656.

Goji NA, et al. 2008. Immune responses of healthy subjects to a single dose of intramuscular inactivated influenza A/Vietnam/1203/2004 (H5N1) vaccine after priming with an antigenic variant. The Journal Of Infectious Diseases198 (5): 635-641.

Isoda N, et al. 2008. Potency of an inactivated avian influenza vaccine prepared from a non-pathogenic H5N1 reassortant virus generated between isolates from migratory ducks in Asia. Archives of Virology epub ahead of print, no volume or pagination yet assigned.

Kalthoff D, et al. 2008.Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans. Emerging Infectious Diseases 14(8):1267-1270.

Kandun, IN et al. 2008. Factors associated with case fatality of human H5N1 virus infections in Indonesia: A case series. The Lancet epub ahead of print, no volume or pagination yet assigned

Nagarajan S, et al. 2008.Isolation and pathotyping of H9N2 avian influenza viruses in Indian poultry. Veterinary microbiology epub ahead of print, no volume or pagination yet assigned. DOI: 10.1016/j.vetmic.2008.06.013

Perrone LA, et al. 2008. H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PloS Pathogens 4 (8):e1000115.

Peyre M, et al. 2008. Avian influenza vaccines: A practical review in relation to their application in the field with a focus on the Asian experience. Epidemiology And Infection 14: 1-21.

Poland GA &S Ambhara S. 2008.Vaccines against Influenza A (H5N1): Evidence of Progress. The Journal Of Infectious Diseases 198(5):629-631.

Rappole JH & Hubalek Z. 2006. Birds and influenza H5NI virus movement to and within North America. Emerging Infectious Diseases 12 (10):1486-1492.

Saito T, et al. 2008.Pathogenicity of highly pathogenic avian influenza viruses of H5N1 subtype isolated in Thailand for different poultry species. Veterinary Microbiology epub ahead of print, no volume or pagination yet assigned. DOI: 10.1016/j.vetmic.2008.06.020

Stelzer-Braid S, et al. 2008.A commercial ELISA detects high levels of human H5 antibody but cross-reacts with influenza A antibodies. Journal of Clinical Virology epub ahead of print, no volume or pagination yet assigned. DOI: 10.1016/j.jcv.2008.06.012

Stevens J, et al. 2008. Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. Journal of Molecular Biology 381(5):1382-1394.

Suriya R, et al. 2008.Seroprevalence and risk factors for influenza a viruses in pigs in peninsular Malaysia .Zoonoses And Public Health 55 (7):342-351.

van der Laan JW, et al. 2008. Animal models in influenza vaccine testing. Expert Review Of Vaccines 7 (6): 783-793.

Vong S, et al. 2006.Low frequency of poultry-to-human H5NI virus transmission, southern Cambodia, 2005. Emerging Infectious Diseases 12 (10): 1542-1547.

Vong S, et al. 2008. Environmental contamination during influenza A virus (H5N1) outbreaks, Cambodia, 2006. Emerging Infectious Diseases 14 (8): 1303-1305.

Waicharoen S, et al. 2008.Influenza viruses circulating in Thailand in 2004 and 2005.Japanese Journal of Infectious Diseases 61 (4): 321-323.

Tony Stankus [email protected] Life Sciences Librarian & Bibliographer

University of Arkansas Libraries MULN 233 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

HIV/AIDS: Progress in Prevention As Reported in The Lancet.

A great service is being provided to readers of The Lancet via a number of highly readable review articles and commentaries on HIV/AIDS prevention strategies and their relative success rates. See full references below for a full and careful reading, but until then, here are some highlights.

Condoms for Men

The first line of defense, apart from abstention, continues to be the use of the male condom.  It appears to be 85%-95%  effective when used consistently. The problem with the missing percentage points appears to be mostly their selective use, in the sense that many men who are having sex with prostitutes will use them  all the time, but will only use them with their wives when they feel there is a good chance of the wife becoming pregnant otherwise. In other words, many men eschew their use during their wives menstruations, when they perceive the chance of pregnancy are minimal. Not only is this a somewhat shaky proposition in terms of birth control, but it exposes the men to HIV picked up by the wife from other means, or it allows HIV which the men picked up , but of which the men were unaware, to be transmitted to their wives.

Condoms for Women

While many are unacquainted with them, female condoms  are in use as both contraceptive and HIV preventive  methods.  They are somewhat less effective, not so much because their construction in theory is in any notable way highly penetrable to the AIDS virus, but because  female condoms can be somewhat awkward  to insert and keep in place.  Female condoms   generally consist of a  flexible cylinder  or sheath of thin latex or polyurethane, with a reinforced ring, largely of the same material as the rest of the sheath, and somewhat reinforced material at the tip that goes into the vagina. Those structures help the female condom stay in place during intercourse.  At the opposite end, at the  vagina’s entrance, is another ring of reinforced material, acting as an anchor , or it might be in something like a  triangle shape. In either case it is open, as opposed to closed off as its opposite end,  and it is through this entryway where the man inserts his penis and into into the connected tunnel or barrel of which, the man ejaculates his semen, and any concomitant viruses.  The greatest advantage of the system is that the woman is in charge of the insertion and use, and can place it inside her even before her partner has an erection.  Women have generally reported either no decline in their sexual enjoyment in using them, and some have reported enhanced sensation. Perhaps unfortunately, their costs are greater, and field trials have generally shown that training women to insist on their partner’s use of  male condoms has about the same level of AIDS preventive effectiveness.

Diaphragms and Cervical Caps with Antiviral Lotions or Lubricants

While there is little doubt that these would not be as effective as either male or female condom use, because they expose more internal tissue to possible viral penetration, use of diaphragms or cervical caps with antimicrobials and newly developed antiretroviral  gels or creams may yet prove to be a reasonably effective strategy. Its advantage for women is similar to that of the female condom, but without the chance  of having the male partner see the external ring at the vulva (and presumably have an opportunity  to object).

Treating Other STDs

Public  health programs where examination, testing, and treatment for other STDs are made readily available, has some effectiveness in HIV prevention, largely because HIV appears to become more readily established or better established in persons with STDs. This is particularly the case if the region is not already saturated with HIV positive patients. 

Encouraging Circumcision of Men

(and Stopping the Detestable Practice of Female Genital Mutilation Masquerading as Circumcision)

Males who are uncircumcised have a somewhat greater risk of developing both sexually acquired and fairly routine bacterial and yeast infections of their foreskins and the underlying penis. This risk increases in countries where daily bathing and hygienic washing of the foreskin-retracted and exposed penis are not   common.  Secondary HIV virus penetration is more likely when even small surface ulcerations emerge, even if the primary infection is self-limiting.   Of course, the use of truly sterile technique is required for any cutting procedure, and this is particularly rarely observed in countries where female genital mutilation is practiced. The latter procedure may well cause a greater risk of HIV owing to both the operation itself, and owing to the follow on infections and chronic irritations. Male circumcision by contrast leads to a penis whose skin is actually toughened after healing and less likely to be penetrable by the virus.

Treating the HIV Infected Partner May Reduce the Risk to an Uninfected Partner

There is some thought and a few clinical trials that suggest that aggressively treating the HIV infected partner and keeping that partner down to a clinically very low or undetectable HIV load significantly reduces the chances of the uninfected partner getting the disease, but this seems to depend on a highly conscientious prescription medication regimen being maintained by the HIV-positive partner, even though the viral load seems extremely low.  Alternatively, it has been suggested that giving the non-positive partner antiretrovirals may be of some use, although this raises the risk of increasing strains of HIV that are drug resistant, and may have other adverse consequences.

Vaccines

There is no easy way to say it. Things are not promising.

The Idea that Retrovirals Will Simply Wipe AIDS Out Making Prevention Unnecessary.

Even with the massive infusion of monies today, five new cases emerge for every two that are started on retrovirals. We cannot, one article in this series quotes, “treat our way out of this crisis.”

Horton R & Das P. 2008. Putting   prevention at the forefront of HIV/AIDS. The Lancet 372 (9637): 421-422.

Merson MH et al. 2008. The history  and challenge of HIV prevention. The Lancet 372 (9637): 475-488.

Padian NS et al.  2008. Biomedical interventions to prevent HIV infection: Evidence, challenges, and way forward.  The Lancet (9638): 585-599.

Tony Stankus [email protected] Life Sciences Librarian & Professor

University of Arkansas Libraries MULN 233 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

Tryptophan: Much More Than Something in Turkey That Allegedly Makes You Sleepy After Thanksgiving Dinner

Tryptophan is an amino acid that is not readily synthesized in the body, but it is an important ingredient in the synthesis of some vital proteins, and therefore must be obtained through dietary intake.

The most common notion most of us have with respect to tryptophan is that it is present in turkey ----which is correct---- and that it makes us sleepy after it is eaten. 

This is not quite the whole truth if you consider that it is the tryptophan that is acting alone. Particularly if you think that the alcohol, copious carbs and fats in need of digestion, and the exhaustion of most holidays, play no significant  supporting role.

The demonstration of this sort of benevolent half-truth  of turkey as a particularly effective sleep-inducer lies in the fact that other foods actually have more tryptophan.

Trypophan is more abundant in edamame (salad bar soybeans), several aged cow’s milk cheeses (most notably Parmesan), and pork chops. Moreover, beef, salmon and lamb have only about 5% less tryptophan; a few bites more of them, and you’re at the same level of tryptophan.

If the tryptophan in turkey was the sole sleep-inducer, you might expect that there would be accounts of a similar effect from consumers of  soy, cheese, roast beef, and pork and lamb chops. This is particularly since there is absolutely no structural or metabolic differences in the tryptophan from any of these sources.

Nonetheless, there is some clinical evidence that the somewhat more concentrated doses found in over-the-counter tryptophan have helped people with insomnia fall, and stay asleep. Nonetheless, those largely loosely-structured   studies fail to cause it be widely recommended by most sleep clinicians and researchers.

But tryptophan deserves more and better press than it gets around the holiday season in any case.

Tryptophan plays other very serious roles in psychiatric disorders, immunology in both cases of infection and in transplant rejection, in smooth function of the gastrointestinal system, and perhaps even in cardiovascular disease.

Tryptophan can do all these things for two very good reasons.

First, tryptophan is a key player in cell membrane biology.  The gateways through the cell, ionopores, tend to be ringed with proteins whose tryptophan-rich heads are prominent, and they are seemingly important to the cell’s input/output balance and function. The tryptophan-based protein most studied of late has been gramicidin, and it has yielded some interesting results.

Second, tryptophan is the most notable precursor to a number of other, better known regulatory proteins.

The Tryptophan/Serotonin Connection

The first of these tryptophan-based regulators is serotonin, the most important player in the management of depression and a number of other brain disorders. These include various types of dementia and Alzheimer’s Disease.

Abnormalities in the body’s handling of tryptophan have also been found in patients with anorexia and bulimia, as well as those made sick to their stomachs and unlikely to want to eat, owing to liver toxicity, kidney failure, or advanced wasting diseases such as seen in cancer patients. Curiously, the relative lack of tryptophan in these cases, sometimes reduces the normal breakdown of serotonin, sometimes giving the afflicted person a peculiar sense of well-being.

Unfortunately, this effect wears off until even more self-starvation or binge-purging takes place, to such a degree that the momentary serotonin lift is once again realized.  The price for this deprivation is ultimately protein starvation owing to a lack of the essential tryptophan needed for other purposes.

There has been growing interest in the use of the Acute Tryptophan Depletion or ATD  test as a challenge of the brain’s ability to manage its serotonin levels.  A  cocktail is given that is deficient in tryptophan, after which in the course of a few hours, generally causes a competition within the body for the remaining tryptophan.

In these cases, the serotonin levels also plummet, deprived of their most direct precursor, tryptophan, by the body using it up for other purposes.

Nonetheless,  most of the mentally healthy volunteers no significant shift of mood downward was observed.

However, in depressed patients   that had been doing quite well based on serotonin modulating antidepressants, mood notably sank.

The surprise was that notably depressed patients who had gained no relief from those drugs, did not have their mood change notably . In other words, they did not get even more depressed, nor did their mood improve. Their form of depression might not be amenable to an adjustment of the tryptophan/serotonin metabolic pathway.

There were some peculiarities. Women tended to be represented more heavily among those whose mood sank with the ATD test, as did persons who had prior thoughts or attempts of suicide.

Most significantly, the small number of persons who were mentally healthy, but whose ATD test caused a severe mood shift downward, contained a high percentage of persons whose family members had depression, or were persons for whom genetics tests had indicated an anomaly that would predispose them to tryptophan-serotonin miscues that might sooner or later trigger depression in them, despite their current upbeat state. It has been recently suggested in a 2008  review  by Fisher et al. in the American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, that a propensity for mistakes in the metabolic pathways by which tryptophan is managed,  has a strong genetic component and may indeed be hereditable.

The ATD test may prove to be a good indicator test, then, of people who would be helped or not, with serotonin-modulating drugs.

It has also been shown that the ATD test increases aggression in hyperactive children, suggesting that this condition too might involve a tryptophan-based metabolic disorder.

Further, after an ATD challenge test in healthy adults, tests of memory and task performance that required the subjects to  make corrective movements or to adjust their responses, showed that the subjects did not seem willing to listen to advice, or otherwise adjust their behavior to improve on their generally dismal  performance.  

That may say something about the ability of people who are depressed being able to take advantage of counseling or psychotherapy in improving their outlook or job performance. Until their tryptophan/serotonin pathway has been fixed, they cannot adapt as well as they should.

The Tryptophan/Melatonin Connection

The second major tryptophan based protein of note is melatonin, which was first found in the pineal gland, a structure very near the brain. Both the pineal and melatonin are best known as a sleep-wake cycle regulators (thereby gaining a modicum of support for tryptophan as a sleep aid, although serotonin which is not made in the pineal, probably play sat least as important a role.) But melatonin is also an antioxidant, and plays a major role in the management of inflammation.

Many of the insights into the anti-inflammatory roles played by melatonin were gained when it was found that melatonin was still being made even after the pineal was surgically removed.

It turns out that the GI tract actually makes much more melatonin, and that melatonin not only plays a role in the regulation of normal (non-spastic, non-ulcerative) colon function, but serves as a cancer protective substance for other visceral organs, most notably the pancreas.

It also  turns out that the aorta of the heart also makes melatonin, and maintaining the correct balance is thought to be a key to avoidance of catastrophic aortic aneurysms.

The Tryptophan/IDO Connection

Some of the body’s biochemicals made with tryptophan have checkered records. The most important of these is indoleamine 2,3-dioxygenase, which is typically abbreviated as IDO.

On the plus side, IDO appears to help the body modulate its immune function in two important instances. First, it plays a role in keeping a mother from immunologically attacking her fetus as an alien invader. Second, stimulation of IDO production has been shown to reduce both bone marrow and other tissue transplantation.

Most intriguingly, having just the right levels of IDO (and therefore just about the right levels of tryptophan) is seen as important to the quelling of autoimmune diseases, particularly certain ones which cause severe nerve pain. Indeed, tryptophan is sometimes suggested as an adjuvant to boost the power of painkillers and antidepressants prescribed for nerve pain.

One proposed beneficial function of IDO is to use up as much tryptophan as possible, so as to deny it to invading organisms, who could use that essential amino acid for their own protein synthesis needs.

Unfortunately, it also appears that the HIV viruses can also stimulate IDO production, and through IDO’s immunomodulatory effect, limit the ability of the body’s T-cells to go on the attack against the invaders.

Something similar appears to be true of the plasmodia parasites that cause malaria. Initial attacks by the parasite appear to stimulate just enough IDO production that the weaker plasmodia which are susceptible to quinine, to die off, allowing the more quinine-tolerant ones to thrive. 

Furthermore, when the production of IDO is over-stimulated, a further metabolite, quinolinic acid flourishes, produced via the kynurenine metabolism pathway. Quinolinic acid is a potent central nervous system toxin, and readily penetrates the blood-brain barrier.

In conclusion, when you think about tryptophan, you’re thinking and functioning with tryptophan. Tryptophan is playing a role in your mood,  your immunity, and many more bodily and mental functions than you might ever had imagined before.

So, go ahead, and eat your turkey. You’re going to need the tryptophan!

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