Sherlock sent me another study published last month in “Psychopharmacology” and titled Antidepressant activity of curcumin: involvement of serotonin and dopamine system. See abstract: http://tinyurl.com/5loqab. The study begins with the familiar rundown of the various healing effects of curcumin (antimicrobial, hypoglycaemic, antioxidant, anti-arthritic etc.). It also mentions curcumin’s rapid metabolism and poor bioavailability, about which I have written quite a bit. This is followed by the detailed description of this new (to me) effect of curcumin.

 

The researchers cite a study (abstract: http://tinyurl.com/5xolvg), published in 2005, in which the Chronic administration of curcumin has been reported to exert antidepressant-like action in olfactory bulbectomy model of depression in rats. I admit that I had to look up “olfactory bulbectomy.” I almost wish I hadn’t! Tender-hearted readers, please skip the next paragraph. All the others may read on.

 

This procedure removes the olfactory bulbs in rats. In other words, these animals are deprived of their sense of smell. Surprise surprise, this leads to behavioural abnormalities such as hyperactivity, which can be resolved by administering antidepressants.

 

Some of those same 2005 researchers continued to do research on this topic, publishing another study three years later (see: http://tinyurl.com/62lk79), but the exact mechanism of its antidepressant activity still remains to be explored. The antidepressant activity of curcumin, i.e. That is what this more recent study sets out to do.

 

Skip, skip, skip through the unintelligible (to me) parts of the study…and also, ugh, through the description of what tasks the mice are forced to perform…the mice are then killed so that the curcumin levels in their brains can be measured, oh dear, this part is a bit gory…skip, skip, skip! If anyone would like to read the whole thing, though, just let me know. I would be happy to forward the study upon request.

 

I did gather the following: when taken together, curcumin and piperine (=black pepper extract) increased the levels of curcumin in the brain, as opposed to curcumin by itself. That makes sense.

 

The study then goes through a detailed list of which antidepressant drugs were administered to the mice…when, how much, etc. This part was also not easy to follow, since I don’t know any of these drugs by name and have no time to look up what they are. More skipping.

 

In the Discussion part we get to the essence of the study: Our results demonstrated a consistent antidepressant-like activity of curcumin in two classical models of depression in mice, namely the forced swim and reserpine-induced immobility models. The researchers found that the effect of antidepressant drugs was stronger when administered to the mice together with curcumin. After reading this, I thought that this synergistic effect might be important in the future treatment of depression.

 

Another finding: The neurochemical analysis revealed that curcumin (20–80 mg/kg, i.p.) dose dependently increased the serotonin (5-HT) levels. It also increased the levels of dopamine but the effect was observed only at higher doses. Further on, we read that The view that 5-HT has multiple functional roles in depression is supported by the clinical and experimental evidences suggesting that the neurotransmitter (serotonin) is involved in the regulation of mood, sleep, memory, learning, and sexual behavior, all of which are deranged to varying extents in patients with severe mental depression.

 

So curcumin increases the levels of serotonin, and that is part of its antidepressant activity. Another part concerns its effect on dopamine, a neurotransmitter that affects important brain processes controlling movement and emotional responses (etc.). I read that dopamine has become an important target of antidepressant drugs. The researchers found that these particular drugs are potentiated by curcumin. And, at higher doses, curcumin by itself also significantly increased the brain dopamine levels. Good stuff!

 

The following quote is for the more scientifically-minded: Based on the present observations, curcumin, at low doses, increased brain serotonin levels via inhibiting its metabolism (MAO-A enzyme inhibition) without significantly affecting the levels of norepinephrine. At high doses, it inhibited the metabolism of dopamine (MAO-B enzyme inhibition) which in turn resulted in the increase in central dopamine levels. Both these activities of curcumin, i.e., by enhancing the availability of serotonin and dopamine in the brain, are responsible for its antidepressant activity.

 

Brief summary: curcumin can enhance the levels of serotonin AND dopamine in the brain, thereby reducing depression.

 

The poor absorption of curcumin is mentioned again toward the end of the study. The researchers found that curcumin absorption was enhanced when piperine was added. The study thus concludes as follows: the coadministration of curcumin and piperine may provide a useful natural adjuvant in the antidepressant therapy.

 

Perhaps my daily intake of eight grams of curcumin is one of the reasons that I am so bloody positive most of the time. I mean, I have always been an upbeat, glass-half-full kind of gal, but maybe my intake of curcumin in the past two and a half years has increased my “happiness” level.

 

In any event, it’s always interesting to discover another unknown (to me!) effect of curcumin. And as far as this particular one goes, I am not complaining!

I went to see my family doctor this morning. I ADORE this wonderful man…he’s an absolute genius. Furthermore, he is very attentive and caring (without going overboard). And honest and upfront. This is the kind of doctor that everyone should have.

 

At any rate, I didn’t tell him beforehand what I thought about my tests but let him read through my results and draw his own conclusions (he would have done so, anyway). Basically, he told me what I already knew, but it’s always good to have a brilliant doctor confirm your assumptions, right?

 

My high blood viscosity value (the test is ESR, in English) did not worry him in the least. He said that that high number would almost certainly be lower if I were to take that test now. Just as I thought. Yippeewee!!!

 

He looked at all my other numbers and asked me what a few of them had been back in April. Most have not varied more than 4 %. For instance, my M-spike has gone up less than 1%. Well, he told me that a minimal variation such as that one is not significant, since test results are not 100% exact. Comforting…I suppose!

 

Conclusion: I am stable. Stable. Stable! STABLE!!! And, consequently, so is Sherlock, whose tests are more or less similar to mine (in terms of variation). Ah, there is much to celebrate today…but only after I prepare my classes for tomorrow! Ciao!

While I was away on holiday, a blog reader, thank you! , left a comment here about a report, published in August, on the development of a spice-based compound that can stop cancer cells from proliferating and even kill them. And guess which spice is involved in this process? Yep, turmeric!

 

You can read the full Science Daily article here: http://tinyurl.com/6f4jll. The scientists working on this project are using organic chemistry, computer-aided design and molecular biology techniques. Computer-aided design…well, well, how about that?

 

So far they have created 40 compounds mainly for use in fighting breast and prostate cancer, emphasizing the synthetic molecules that appear to have the most potential to serve as the basis for anti-cancer drug development.

 

An important statement: according to the lead researcher, James Fuchs, most of the compounds we’ve made have been more potent than curcumin against the cancer cells. More potent than curcumin. Intriguing! I am looking forward to seeing more published on this topic.

Well, okay, I was hoping for better…I was hoping for outstanding and extraordinary…yes, I was hoping for dazzling results.

 

But the tests that Sherlock and I had on July 31^st, at the end of our resveratrol experiment, are quite a bit less than dazzling. A first glance at my results turned me into Ms. Glum. I simply went to bed (it was bed time anyway)…all gloomy and doomy. In the morning, after a more careful perusal, I realized that my results weren’t THAT bad. Then, once Sherlock and I had finished comparing our tests point by point, I started feeling much better. Why?

 

Because she and I are still stable. What could be more important than that? I will take “stable” over “dazzling” any day. Well, okay, to be completely honest, I wouldn’t have minded glittering just a wee bit.

 

For some reason that puzzles us, though, our blood viscosity shot way up. Mine is the highest it has ever been: 97 mm/hr (the top end of the range is 30!). Sherlock’s blood viscosity went up quite a bit, too, though not as much as mine. I have my own theory about this sudden increase.

 

Preamble (to the theory): in July I began taking a homeopathic remedy that Sherlock has been taking for quite a long time and that is supposed to prevent bronchitis. She, in fact, hasn’t had a case of bronchitis in years. So, since my lungs seem to be my weakest spot, I asked my family doctor if I could take it, too. He said, “sure, go right ahead.” You have to take this remedy every day for the first ten days of the month, for three months, preferably beginning in June. The conscientious, meticulous Sherlock began in June. I, the disorganized procrastinator, in July.

 

Thing is, as soon as I begin taking this remedy, I had an almost immediate reaction to it, in the form of a runny nose and a sniffle. The same thing happened in August and now in September. No big deal, though.

 

My theory: could it be that my teeny tiny but feisty immune system had a reaction to the remedy? Since the blood viscosity value (=VES, in Italian) is an inflammation marker, I suspect that my recent high VES value could have been caused by the stimulation of my immune system. This is just a feeling, mind you. It could just be a freak result, as a friend told me. Or it may have been affected by other variables, such as the hot weather or testing conditions. In fact, a doctor friend of mine told me that the end of hot July is not the best time to have tests done. Ah. Anyway, who knows…I will ask my family doctor on Thursday for his opinion, too.

 

Other items. My hematocrit is slightly below the normal range for the first time ever. So are both my red and white cell blood counts. Just slightly, though. I am not too concerned about it.

 

Worrisome trend: my IgM has been going down a teeny tiny bit with every test. It is now 0,08 (the low end of the normal range is 0,40). What happens if it disappears altogether? Is that a possibility? And is there a way to increase that number? Hmmm…more things that I must investigate.

 

An oddity: even though both curcumin and resveratrol are supposed to lower cholesterol, my total cholesterol shot up to a second, all-time high. Hello?!!! Was it caused by the ice cream I ate during the heat wave in July? No idea.

 

But there is some good news, of course. My monoclonal component went down from 28.1 to 27.7 %. My total IgG went down a wee bit, but, more importantly, my M-spike shows very little change (a fraction of a fraction upward, from 2.44 to 2.46) since my last set of tests. Sherlock’s M-spike went up a bit more than mine, but it has been higher in the past…

 

These are the main things. My results show no significant changes in B2M, LDH, etc., so I won’t bother listing those (all within the normal range, as usual, anyway).

 

What is our conclusion? Well, we are a bit disappointed but also happy to be stable. The main value that Sherlock and I will be monitoring closely in our next set of tests will obviously be our blood viscosity. I am convinced that it will go down, though. 

 

A question just popped into my head: did we take enough resveratrol (one gram a day) to make a difference? Hmmm.

 

Well, even though these results show no incredibly positive trends, there are also no incredibly negative ones. So we both continue to amble along the path of stability. That’s what matters.

 

P.S. Sherlock and I will be taking more or less the same things (curcumin, quercetin and fish oil) until we have our next set of tests in late October. 

 

Together, just like the good friends that we have become.

The other evening Stefano arrived home from work and asked: “there is an amazing cloud in the sky, have you seen it?”

 

“No,” I answered.

 

We went outside. For a few minutes, until the tiger mosquito “clouds” sent us hurrying back inside, we stood side by side, gazing in admiration at a huge, odd-shaped cloud illuminated by the setting sun.

 

Hand in hand, like little kids.

Yesterday, as I do on an almost daily basis, I checked out other myeloma blogs to see how my fellow bloggers are doing. Well, I wish to thank Teresa (“The Beast” blog) for leading me to Randy Pausch’s “Last Lecture.” You may have heard about the talented computer science professor at Carnegie Mellon University who delivered a lecture in September 2007 titled “Really Achieving Your Childhood Dreams.” The lecture has been seen by millions on YouTube.

 

Prof. Pausch had pancreatic cancer. His last lecture was literally his last. He died in July 2008.

 

I urge you to watch it when you have slightly more than an hour of free time…you won’t regret it (I think): http://www.thelastlecture.com/aboutr.htm. This link will take you to a page where you can read a bit about Prof. Pausch, his work, pancreatic cancer, etc. Click on “Randy’s website” (or here: http://tinyurl.com/2brkxr) to find a series of videos, including his brief testimony before Congress and…his last lecture.

 

I laughed out loud, I teared up, I listened. I learned. Early in the lecture he tells the audience that We can’t change the cards we’re dealt, just how we play the hand. Indeed! He then focuses on his childhood dreams. While listening to his words, I tried thinking of my own childhood dreams. Not much came to mind, oddly enough, but I did recall spending hours putting jigsaw puzzles together as a kid (this is pertinent, as we will see). The more difficult the puzzle was, the more pieces it had, the better. The absolute best was putting together 5000-piece puzzles. I still love puzzles, and would have one spread out on a table right now…if we didn’t have cats, that is!

 

In fact, and this is a brief aside, my early enjoyment of elaborate puzzle-solving explains a lot about who I am today—my curiosity, my desire to learn and do research about practically everything under the sun. Of course, now I have an extra “push”—the quest to save my life and (I hope!) help others in the process. My childhood dreams certainly never included developing myeloma! But what is myeloma if not a big and daunting puzzle…the most difficult puzzle of all, in my experience???

 

Anyway, and here I get to the point (!), the first childhood dream that comes to mind is related to my love of puzzle-solving: I wanted to become an art restorer. The idea of bringing ancient paintings back to life was fascinating to me. Well, I never did go into the art restoration field…my life took other turns.

 

Then there was the “Margaret the Archaeologist” phase…another example of how nerdy I was even as a child. At the age of ten or so, I became obsessed with the “mystery” of the Etruscan language. I was certain that I would grow up to be the first to unlock the secrets of that ancient language.

 

My parents took me to many of the Etruscan sites and museums all over Tuscany and waited patiently while I painstakingly copied tomb inscriptions and the baffling symbols I found on urns (etc). I still have my Etruscan notebooks in a sealed box somewhere. Well, I never did find the solution to the Etruscan puzzle, but when I went to college in the United States I took some archaeology courses as part of my major in Social Anthropology…and I wrote a paper about the Etruscan civilization and language. So even later on in my life I had a connection to this particular childhood interest. Still do, in fact. I love visiting ancient sites, Etruscan and non-Etruscan.

  

I don’t recall having any childhood dreams as creative as Prof. Pausch’s dreams of being Dr. Kirk (Star Trek) or experiencing zero gravity. The closest thing would be my longing to sprout wings on command and be able to fly. I still dream about flying, but I have in recent years added the ability to become invisible so hunters won’t shoot me down…hey, you’ve got to be practical, after all! 🙂

 

Well, I don’t want to harp too long on this subject. I simply wanted to post about a fascinating lecture that gave me quite a lot of food for thought and will probably be of interest and use to other cancer patients. Prof. Pausch offers a lot of good advice, including the following: never underestimate the importance of having fun. Very true! And I loved what he said about his near-deathbed conversion…but I won’t spoil it, you will just have to go watch the video to hear what happened… 🙂

 

I would like to end the post with a bit of advice that I have taken to heart and that Prof. Pausch talks about in his last lecture:

 

Never lose the child-like wonder.

I already knew that under certain circumstances it is not a good idea to swallow pills with grapefruit juice, but I didn’t know that orange and apple juice have recently joined the no-no list. New research shows that they, too, may limit the body’s absorption of drugs, compromising their effectiveness. I found this quote and more information in a HealthDay News report published on August 19^th: http://tinyurl.com/5rrc9e.

 

So all three juices may lower the body’s absorption of some medications. Lower? Hmm, this is not good news at all. The HealthDay News story provides a list of medications that are affected by the three juices, by the way.

 

I used to swallow my curcumin capsules with grapefruit juice (or even a whole grapefruit) whenever possible because I thought, or hoped!, based on my readings, that the latter might increase the bioavailability of the former. I knew, though, that it isn’t a good idea for certain drugs (chemotherapy, e.g.) to be lingering in your bloodstream. But with curcumin we have the opposite problem…oh well, no more juice around pill-taking time from now on.

 

In sum, to be on the safe side, the best way to swallow any sort of pill seems to be with water…full glasses of water, not just a few sips. At the end of the HealthDay News report, I learned that it’s also best to drink cool water, not hot, because your stomach empties cool water faster, sending the medication on its way to the small intestine and finally the blood stream. Ok, I didn’t know that. So tea is out, too, I guess. So much still to be learned…

I read a fascinating news report earlier today. A Massachusetts resident who has been suffering for the past 12 years from the painful after effects of a famous case of salmonella poisoning began sprinkling turmeric on her food a couple of months ago. Well, her life has changed. For the better.

 

She can now do things that she wasn’t able to do before, such as vacuum the floor. And here I do feel compelled to comment that it is a tad beyond my comprehension how vacuuming the floor could possibly be viewed as a positive thing…!!!

 

Seriously, though, this is a very interesting story, published on August 15^th, see: http://tinyurl.com/5nzu5d. And it gives us a further example of the importance of spicing up our food!

This morning I read some of the PubMed Alerts that I received during my absence. One of them led me to the abstract (see: http://tinyurl.com/5wrw5p) of a recent study on quercetin and prostate cancer cells published in “Prostate” at the end of August.

 

The researchers wanted to evaluate the effect(s) of quercetin on normal and malignant prostate cells and to identify the target(s) of quercetin’s action. Their results have implications for myeloma, too, as we will see later on: Our findings demonstrate that quercetin treatment of prostate cancer cells results in decreased cell proliferation and viability. Furthermore, we demonstrate that quercetin promotes cancer cell apoptosis by down-regulating the levels of heat shock protein (Hsp) 90.

 

Quercetin killed the malignant cancer cells by inhibiting this thingie called Hsp90, but did no harm to the normal prostate cells.

 

As their name suggests, heat shock proteins protect cells that are exposed to dangerously high temperatures. They are also triggered when, for instance, our cells are exposed to infections or toxins (etc.). But, and there is a BUT!, they can also be essential to the survival of cancer cells. You can read more about this process in Wikipedia: http://en.wikipedia.org/wiki/Hsp90 (scroll down to “Cancerous cells”). Inhibition of Hsp90 has thus become an important area in cancer research.

 

The main reason I am reporting about Hsp90 is that I found that it is a target of conventional myeloma treatment as well. I located several studies on the involvement of Hsp90 in the survival of myeloma cells, such as this one, published in August 2008 in “Leukemia”: http://tinyurl.com/59k4g8. It confirms that this particular heat shock protein is over-expressed in myeloma cells and critically contributes to tumour cell survival. Definitely not good!

 

A pertinent aside: a quick search of the Clinical Trial website revealed that there are currently three clinical trials involving multiple myeloma and two different Hsp90 inhibitors in combination with Bortezomib (Velcade). Two of the trials are still recruiting, the other is active but not recruiting. Interesting.

 

In conclusion, our (Sherlock’s and mine) most recent experiment did not include any quercetin, but I had already planned to resume taking it after the summer holiday. And so, last week, I added one gram of quercetin to my regular protocol.

 

After reading the Hsp90/quercetin abstract this morning, I am very happy I did so!