As I am stuttering through recovery from LungMutiny2010, I am paying more attention to my diet. So, as I try to go out for my 10 min walk everyday, I still drink some sports drink – usually Gatorade made from the massive vat of powder you can buy here at Costco.
We tend to get plenty of sodium in our diet – far too much in the US, actually – but I always worry about potassium when I am sweating (Disclaimer: I am not an exercise physiologist or a cardiovascular or nephrology physician.).
I always thought that the widely-sold sports drinks were the best sources of potassium outside of eating bananas or some dried fruits.
So, I was surprised to learn that an 8-ounce serving of orange juice contains 18-fold more potassium than an 8-ounce serving of Gatorade® (450 mg vs. 25 mg).
I suspect that this is a Good Thing when exercising but perhaps a concern for hypertensive patients who must monitor their potassium levels.
Is there anyone with more practical knowledge about potassium and physiology willing to weigh in?
Is a dilute, no-pulp orange juice (maybe 1:1 with water) a good adjunct to a sports drink when carrying multiple bottles of beverages on a bike ride or trail run?
Have you ever taken one of the now-over-the-counter heartburn relief remedies like Tagamet, Zantac, or Pepcid?
How about the beta-blocker atenolol (Tenormin) or metoprolol (Lopressor) for antihypertensive therapy, or the original less-selective beta-blocker propranolol (Inderal) for migraines, presentation anxiety or stage fright?
If you answered yes to either question, you owe a debt of gratitude to Sir James Black, the Scottish physician who left us earlier this week at age 85. The best obituary I have seen memorializing Sir James comes from the UK Telegraph.
Black was called the father of analytical pharmacology and was said to have relieved more human suffering than thousands of doctors could have done in careers spent at the bedside. Certainly, no man on earth earned more for the international pharmaceutical industry.
Yet though he became joint winner of the Nobel Prize for Medicine in 1988, Black derived little personal financial benefit from his discoveries. Among businessmen he had a reputation as an irascible maverick and this prickly independence, combined with an antipathy to big institutions, led him to flounce out of jobs whenever he felt corporate short-sightedness was getting in the way of research.
Others can be read at The Independent, The Times, The Guardian, The Scotsman, and BBC News.
It is rare for a scientist to discover one drug that makes it to market. Sir James not only led the discovery of two major drugs, propranolol and cimetidine. As if that were not enough, each drug was a “first-in-class” agent, the first approved drug that acts via a novel mechanism of action.
Although I saw this obituary over the weekend, I didn’t get to posting it until today. I was reminded by a local friend, an outstanding young scientist in her own right, of the impact that Dr Schanberg had made on so, so many lives in science, medicine, and our larger community.
I only had the honor of meeting Dr Schanberg once, shortly after his cancer diagnosis, while we were at a Duke Cancer Patient Support Center fundraising dinner. His wife of over 50 years, Rachel, is founder and former director of the organization which they started following the loss of their own daughter.
Among the many scientists and physicians that were mentored by Dr Schanberg is my dear friend and colleagues, Dr Cindy Kuhn. I knew that Dr Kuhn had worked with Dr Schanberg extensively, having co-authored 83 publications. What I had not appreciated previously was that Cindy had also done her PhD work with Saul – so much for that rule of distancing oneself from one’s mentor.
I can’t do any better than the obituary that follows.
“Saul was a warm and wonderful, high-spirited, opinionated and good humored man much loved for his infectious enthusiasm for science, his love of Duke (and Duke basketball) and most importantly his commitment to his family and friends.”
And I couldn’t live a life any better than that.
After writing this post, I came across Alex’s obituary and guestbook on Legacy.com. By all accounts, Alex was a great kid – loved and admired by many – an accomplished hockey player and musician with a love for the mountains. This could have been you or I, or worse, one of our own children.
Breaking my heart this morning is news from Boulder that last month’s death of 20-year-old CU student, Alexander McGuiggan, was from consumption of “opium tea.”
Police department spokeswoman Sarah Huntley said investigators believe McGuiggan and others had acquired poppy plants — which are available legally over the Internet — and were boiling pods to make intoxicating tea.
Police believe McGuiggan knew that the tea he was drinking was made of opiates, Huntley said.
“What he may not have been as aware of was the dangers of what he was ingesting,” she said.
The Boulder County Drug Task Force is investigating other people who may have been involved in “the procurement of the tea, and the making of the tea,” Huntley said. Those people could face charges, she said.
A previous report has been that the student and friends were boiling up poppy seeds, but I was suspicious as those lack significant amounts of opiates. Instead, as Ryan Morgan of The Boulder Daily Camera reports accurately, the students appear to have obtained seeds for Papaver somniferum, and grown plants, and extracted the latex from mature pods. Opium is an alcoholic tincture of the pod latex and is comprised of approximately 10% morphine, 0.5% codeine, and other lesser naturally-occurring opioids (the plant synthesizes these opiates of the “benzomorphan” class in a biosythetic pathway beginning with the amino acid, L-tyrosine.).
The sad fact is that we’ve known for over 200 years that this is a bad idea: based upon growing conditions, harvest time, and extraction method, the resulting concoction can provide an extremely variable dose of these compounds. Used medicinally as one of the strongest analgesics (“painkillers”) we know, in higher doses the opiates can impart a warming sense of euphoria but, at even higher doses, suppresses the respiratory control center of the brain stem, resulting in death.
Welcome 4 March readers of The Daily Grail – please be sure to also click on the original post about the DMT article by my colleague, Laura Mariani.
Thanks to Dave Munger & Co’s ResearchBlogging.org, I just found a fabulous neuroscience grad student blogger from Emory University: Laura E Mariani at Neurotypical?
Doctor-to-be Mariani blogged last Monday about a paper in Science where the endogenous ligand of the orphan sigma-1 receptor was identified as the hallucinogen, N,N’-dimethyltryptamine, or DMT. The work originated with the group of Arnold Ruoho and colleagues at the University of Wisconsin’s Depts of Pharmacology and Physiology, together with a collaborator at the Isfahan University of Technology in Iran.
As an aside, what blows me away is that the first author on this publication, Dominique Fontanilla, is a graduate student in the UW Molecular and Cellular Pharmacology training program. The funding acknowledgment suggests that she was on an NIH institutional training grant and then scored her own individual predoctoral NRSA from the National Institute on Drug Abuse. It appears that she also has a background in synthetic chemistry that extends back to her Sigma Xi-recognized undergraduate work at Carleton College in Minnesota. If anyone is looking for a stellar postdoc candidate in this field (*cough* DrugMonkey), you’d better get in line now.
Anyway, as a neuroscientist, Laura tells the story far better than I can so you should go to her post to read the details.
Where a natural products cancer pharmacologist gets interested in this story is its intersection with plant-derived medicines – 25% of today’s pharmaceuticals can be traced to natural sources, I recognize that the history of my discipline lies in the ethnobotany of indigenous cultures and their religious and ritual use of plant compounds with hallucinogenic effects of other activities in modulating the central nervous system. Hallucinogens used culturally in religious rituals are often called entheogens (loosely translated as “creating god within”).
The 2008 Nobel Prize in Physiology or Medicine has been split between the discoverers of two viruses of major pathophysiological importance.
Half of the prize goes to German Dr prof Harald zur Hausen for his discovery of human papilloma virus as the cause of cervical cancer while the other half went to the French team that discovered human immunodeficiency virus (HIV), Françoise Barr´-Sinoussi and Luc Montagnier.
Just a few early thoughts: Notably absent from the award is American Robert Gallo, whose role in the HIV discovery has been long disputed. That this Nobel can only be awarded to a sum total of three individuals means that the committee chose to honor zur Hausen’s seminal work on HPV rather than acknowledge Gallo’s questionable role on HIV (ouch!). (note added: Perhaps I’m being a little harsh as Gallo and Montagnier acknowledged the roles of each group in Science in 2002; Montagnier cited the crucial contribution of Gallo’s group as the use of a the T-cell growth factor, now known as interleukin-2, for short-term virally-infected cultures. I’m very interested to hear how Montagnier comments on this obvious issue today.)
I will also be interested to see how the HIV-denialist community chooses to spin this award acknowledging the importance of the discovery of HIV as the cause of AIDS. I do not believe that the Nobel Foundation is beholden to Big Pharma or receives proceeds from the sales of HIV diagnostics or HIV therapeutics.
Lastly, I am simply tickled to see Dr zur Hausen recognized for the HPV work, of which much of the early work was conducted with HeLa cells. HeLa is a well-known human cervical carcinoma cell line first isolated at Johns Hopkins from an African-American woman from Virginia with cervical cancer. The engaging story of Henrietta Lacks and her cells has been the focus of writings by Rebecca Skloot (PDF of 2001 NYT article) and will be compiled in her upcoming book, The Immortal Life of Henrietta Lacks.
Congratulations to the professors on these outstanding accomplishments.
A couple of colleagues turned me on the other morning to a press release by researchers at the University of Warwick who recently published in PNAS that their data apparently overturns the Meyer-Overton Rule regarding solubility of a compound in olive oil and its propensity for crossing biological membranes. I’m having trouble understanding exactly why their conclusions are earth-shattering.
At the turn of the last century, Meyer (1899) and Overton (1901) independently conducted experiments to demonstrate that the longer the carbon chain of a molecule, the better it partitioned into olive oil relative to water, and the more potent it would be as a general anesthetic (I’m almost certain that Meyer did his anesthetic work in tadpoles). This is back when we thought that general anesthetics worked primarily by disrupting ion channel function by altering cell membrane structure (it’s actually more complicated than that, involving anesthetic molecules directly interacting with hydrophobic surfaces on ion channels, but the bottom line is that the better a molecule partitions into the lipid portion of the cell membrane, the greater its anesthetic potency. This point only holds true for inhaled gases from nitrous oxide to halogenated hydrocarbons like isoflurane and is unrelated to sedative/hypnotics used in anesthesia that have discrete molecular actions such as benzodiazepines like diazepam or opiates like fentanyl).
The press release from the University of Warwick describes what appear to be really cool electrochemical experiments with ultramicroelectrodes and confocal microscopy that are to be published in the 26 August 2008 issue of the Proceedings of the National Academy of Sciences (PNAS). The research team apparently provides direct evidence that increasing carbon chain length of carboxylic acids (acetic, butanoic, valeric, and hexanoic) cause them to pass through membranes progressively more slowly.
But instead of being at odds with the Meyer-Overton correlation, this is exactly what one would expect from the Meyer-Overton experiments.
The point is that membrane-disrupting anesthetics act primarily by staying in the membrane. (I might add that the press release is vexing to me because it fails to refer to the work of Meyer, calling it the Overton rule, and uses the term “cell wall” instead of “cell membrane.”)
The statin class of cholesterol-lowering agents is rich with history and lessons in the power of natural products, the potential of the prepared mind, and just how precarious the path of drug development can be.
American Scientist, the official publication of the scientific research society Sigma Xi, hosts this issue an absolutely lovely article entitled, “Statins: From Fungus to Pharma.”
Expertly and engagingly written by University of Pennsylvania biology professor Dr Philip A Rea, the article launches with the story of a then-young Japanese biochemist, Akira Endo. (Evidence of my longstanding admiration for Dr Endo goes back beyond my 10 Jan 2006 post, “All hail, Dr Akira Endo.”).
When I first heard that 24-year-old British singer-songwriter Amy Winehouse was hospitalized with early stage emphysema I said “what?” DrugMonkey, a drug-abuse research colleague, has a terrific post up now on the link between Winehouse’s crack cocaine use, possible genetic predisposition, and the emergence of early-onset emphysema.
While sad to see a very young person so afflicted, I tend to be fascinated scientifically by these odd medical cases involving natural products – often drugs of abuse.
I’m also particularly impressed by Amy Winehouse’s tremendous vocal talents and songwriting abilities. Her jazz and soul vocal style has been described as reminiscent of legends like Sara Vaughn and I find it striking that her songs are considered pop music in 2008. But like many incredible musicians before her, Winehouse at 24 has more legal problems, drug abuse issues and violent, self-destructive behaviors than most people might accumulate in several dozen lives. I echo DrugMonkey’s call to Winehouse and her dad that she avail herself ofserious acute and long-term medical intervention, and soon.
So, while my personal output here is a bit slow, mosey on over to DrugMonkey for a lovely medical discussion of the Winehouse emphysema case.
Well, not only am I weaseling out of posting original content today but I’m going to direct you to an excellent repost by Bora Zivkovic at A Blog Around the Clock.
I am often asked why plants expend the bioenergetic capital to synthesize secondary metabolites. In his post, Bora notes that the synthesis of capsaicin by hot peppers results in selective avoidance by mammals but an interesting co-evolutionary relationship with thrashers.
And in other news, mosey on over to the newest member of the ScienceBlogs community, the superb ERV blog written by Abbie Smith, a graduate student in Middle America studying HIV evolution in patients and crafting some of the most magnificient takedowns of evolution denialists that I have seen on the intertubes. Welcome ERV!