Monthly Archives: March 2009

Busy busy busy!

img_9907I have been very busy this week…extra work (translations, mainly) and whatnot. No time to do any serious research/reading. Or answer any messages (sorry about that!).

But I did find a snippet of time to take a photo of Peekaboo on my messy desk…she is looking at my bookcase, probably trying to figure out how to climb up it and retrieve “mousie.” Hehe.

The importance of spelling…

A blog reader (thanks!) sent me this text, which I was able to read immediately and easily. How about you?

 

Title: “Only great minds can read this” (so far, so good…)

 

fi yuo cna raed tihs, yuo hvae a sgtrane mnid too

Cna yuo raed tihs? Olny 55 plepoe out of 100 can.

 

i cdnuolt blveiee taht I cluod aulaclty uesdnatnrd waht I was rdanieg. The phaonmneal pweor of the hmuan mnid, aoccdrnig to rscheearch at Cmabrigde Uinervtisy, it dseno’t mtaetr in waht oerdr the ltteres in a wrod are, the olny iproamtnt tihng is taht the frsit and lsat ltteer be in the rghit pclae. The rset can be a taotl mses and you can sitll raed it whotuit a pboerlm. Tihs is bcuseae the huamn mnid deos not raed ervey lteter by istlef, but the wrod as a wlohe. Azanmig huh? Yaeh and I awlyas tghuhot slpeling was ipmorantt!

 

As usual, I checked Snopes (http://tinyurl.com/nxfw) before posting this text. There is actually a scientific basis (split-fovea processing and so on…don’t ask!) for this “scrambled” reading ability. As long as certain letters are in their “proper places,” that is, almost everyone can comprehend a scrambled text. Not 55 out of 100 (as claimed above), but probably a much higher percentage.

 

But the real reason I am posting about this today is that I came across another text thanks to Snopes. If you really want a challenge, try to read this one (hehe):

Iltnsegnetiry I’m sdutynig tihs crsrootaivnel pnoheenmon at the Dptmnearet of Liuniigctss at Absytrytewh Uivsreitny and my exartrnairdoy doisiervecs waleoetderhlhy cndairotct the picsbeliud fdnngiis rrgdinaeg the rtlvaeie dfuictlify of ialtnstny ttalrisanng sentences. My rsceeerhars deplveeod a cnionevent ctnoiaptorn at hnasoa/tw.nartswdbvweos/utrtek:p./il taht dosnatterems that the hhpsteyios uuiqelny wrtaarns criieltidby if the aoussmpitn that the prreoecandpne of your wrods is not eendetxd is uueniqtolnabse. Aoilegpos for aidnoptg a cdocianorttry vwpiienot but, ttoheliacrley spkeaing, lgitehnneng the words can mnartafucue an iocnuurgons samenttet that is vlrtiauly isbpilechmoenrne.

Good luck!

 

[Give up? You will find the solution here: http://tinyurl.com/2h62m]

International Myeloma Working Group guidelines for free light chain testing in multiple myeloma

Yesterday I received a special edition of the International Myeloma Foundation’s newsletter, “Myeloma Minute,” where I found some interesting details about the serum free light chain (FLC) test.

In September 2008 “Leukemia” published the guidelines developed by the International Myeloma Working Group for serum free light chain analysis in multiple myeloma. The International Myeloma Working Group is made up of 90 leading myeloma researchers from around the world who collaborate on a broad range of myeloma research projects. With a goal to improve myeloma treatment options and diagnostic systems, their work focuses on protocols to provide a more durable remission for myeloma patients while improving quality of life, addressing the needs of both myeloma patients and the physicians who treat them. And the serum-free light chain analysis guidelines are the result of this collaboration.

 

Serum free light chain assays are capable of detecting free light chains at their normal (non-elevated) levels in the blood. Importantly, these assays can detect mildly increased levels of free light chains even when these levels are undetectable by other means of testing. This means that multiple myeloma could be detected earlier and it is particularly useful in instances when only small amounts of light chains are produced by the myeloma.

 

The special edition provides a link to more information about serum immunoglobulin free light chain assays: http://tinyurl.com/dbpecr  

 

The key recommendations from the International Myeloma Working Group’s guidelines are

  • The serum free light chain (serum FLC) assay in combination with serum PEL (serum electrophoresis) and serum IFE (serum immunofixation) is sufficient to screen for pathological monoclonal plasmaproliferative disorders other than AL (light chain amyloidosis) which requires all the serum tests as well as 24 h urine IFE.
  • The serum FLC assay should be measured at diagnosis for all patients with MGUS, smoldering or active multiple myeloma, solitary plasmacytoma and AL amyloidosis.
  • Serial serum FLC ascertainment should be routinely performed in patients with AL amyloidosis and multiple myeloma patients with oligosecretory disease.
  • It should also be done in all patients who have achieved a CR (complete response) to determine whether they have attained a stringent CR.

“Myeloma Minute” also provides a link to the full guideline paper: http://tinyurl.com/c64v5c For obvious reasons, I concentrated on the smoldering, or asymptomatic, myeloma part. It turns out that this FLC test is useful for assessing prognosis for progression in smoldering MM. An abnormal result predicts for higher rates of progression. For other conditions, MGUS and so on, please have a look at the above link.

 

An important excerpt: the FLC assay is of major prognostic value in virtually every plasma cell disorder, including monoclonal gammopathy of undetermined significance, smoldering myeloma, active myeloma, immunoglobulin light chain amyloidosis and solitary plasmacytoma.

 

Well, since I haven’t yet gone to the hospital lab for my blood and urine tests (for reasons that I have explained in a previous post), I am going to ask my GP that this test be added to my never-ending, at this point!, list of tests. Hmmm, as it turns out, it may not always be a bad idea to procrastinate…

EGCG and bortezomib (Velcade): the full study

A blogging friend reminded me about the EGCG-Velcade study published on February 3rd 2009 in “Blood,” and that I posted about here on February 4th. Sherlock (grazieee!) retrieved the full study for me…but then I put it on my desktop and promptly, uhm…forgot about it. That happens. Oh well.

 

At any rate, this morning I read through it to see if there was anything I could add to what we know from the abstract (http://tinyurl.com/c9ppr2). There is.

 

Read this (BZM, by the way, is the acronym for bortezomib, marketed as Velcade): when BZM and EGCG were added together, the cell killing by BZM was completely prevented and cell survival remained at 100% […]. Yikes! This occurred even at low EGCG concentrations. Scary.

 

Another interesting discovery. This study’s findings contrast with previous reports about the cytotoxic (=toxic to cells) effect of EGCG on myeloma cells. The researchers only noted weak cytotoxic effects starting at 20 microM, which become somewhat more pronounced when drug exposure times are increased from 48 to 72 hours. Interestingly, even under conditions where EGCG is slightly toxic, it is still able to potently antagonize the cytotoxic effects of BZM. For example, in U266 cells, 20 microM EGCG alone reduces viability by 20% after 48 hours, and 10 nM BZM reduces viability by >95%—yet, when the two drugs are combined, viability is still only reduced by 20%. By the way, U266 is a myeloma cell line frequently used in these studies. Well, I must say, this bit of news is not encouraging AT ALL…Well, let’s go on.

 

The inhibiting effect of EGCG against bortezomib was observed also in vivo (nude mice with myeloma tumours, poor dears). I don’t need to go into any details, suffice it to say that the in vitro results were confirmed in vivo, too.

 

The researchers tested the antioxidant activity of EGCG to see if that could be the cause of its bortezomib inhibition, but no, that wasn’t it. They did confirm that EGCG is a powerful antioxidant, though, which is good news for green tea drinkers not on Velcade.

 

EGCG’s inhibiting activity is instead apparently due to the presence of boronic acid in BZM: The severe antagonistic effect of EGCG appeared to require the presence of the boronic acid moiety in BZM. Proteasome inhibitors that did not contain any boronic acid were not affected by EGCG. So EGCG has a problem with boronic acid, not proteasome inhibition per se.

 

Ah, in the Discussion part I read something that I didn’t know: Interestingly, it has been reported earlier that vitamin C, a 1,2-diol containing compound as well, is able to antagonize cell killing by BZM. Apparently, vitamin C reacts with the boronic acid contained in bortezomib and, like EGCG, inhibited its cancer killing effect. Not good. Another word of caution: if you are taking Velcade right now, please see also my report on dietary flavonoids and Velcade (scroll down my Pages on the right).

 

Well, this study certainly supports the importance of giving your cancer specialist a list of all the supplements that you would like to take. Especially if you are following a conventional course of treatment, and even more especially (!) if said treatment includes Velcade.

 

The study concludes: In humans, EGCG concentrations of 5–8 microM can easily be achieved after the ingestion of capsules containing GTE (polyphenon E). We therefore have no doubt that our discovery is highly relevant for clinical considerations and would strongly urge patients undergoing BZM therapy to abstain from consuming green tea products, in particular those widely available, highly concentrated GTEs that are sold in liquid or capsule form.

 

In conclusion, if you are currently taking Velcade, do not drink any green tea or take EGCG or vitamin C. You might feel better, but the anticancer effect of Velcade, unbeknownst to you, is probably being severely blunted, if not entirely obliterated. Not good!

 

By the way, I was so focused on the curcumin cell membrane ion channel studies that I completely missed celebrating my two-year blogiversary (=blog anniversary…I just coined a new word…or did I?) on March 17! Has it already been two years? Yep. Amazing how time flies…

Curcumin, ion channels and excited membranes

This is a sort of continuation of yesterday’s post. In his comment, Peter asked an excellent question…my answer is that he is right, that these studies may not help us in practical terms right now, but they do point to the possibility that there is more to the curcumin picture than its well-documented poor bioavailability (when administered orally). The evidence that there may be other mechanisms at work seems to be accumulating…that is, unless I have completely misunderstood the studies that I have been reading recently!

 

The 2006 study (abstract: http://tinyurl.com/awyvv9) that I want to discuss today was sent to me recently by a friend (grazie!). It examines the link between the anticancer effects of dietary compounds and ion channels, which are membrane-bound proteins […] that are present on the surface of various cancer cells and tissues. Heh, and I thought cell membranes were difficult!

 

The activity of these ion channels is essential, it appears, for the progression of cancer…and metastasis. When certain ion channels (VPSCs, or voltage-gated sodium channels) are upregulated while others (VGPCs, or voltage-gated potassium channels…er, don’t ask!) are downregulated, in fact, cancer cell membranes get all excited, in line with such cells’ ‘hyperactive’ behaviour. The activity of ion channels has been found to control/enhance a variety of cellular behaviours that would be involved in the metastatic cascade. Oh boy.

 

The researchers therefore suggest that ion channels may be a major target for the anti-cancer effects of some natural compounds. By the way, an explanation of ion channels can be found at “Ion channels for beginners”: http://tinyurl.com/cae5b6 (see “Things ion channels do,” in particular). And the term “voltage-gated” is explained here: http://tinyurl.com/2lpqmo

 

At any rate, the main point is that the researchers set out to see if ion channels could be affected by a few well-known anticancer dietary compounds. What they discovered is significant, since, as I understand matters, when ion channels are affected, the various processes that lead to cancer progression/mestastasis are essentially stopped.

 

Well, as it turns out, resveratrol affects ion channel activity, thus reducing the excitability of metastatic cancer cells. So does curcumin, even though more evidence is needed for the latter, according to the study. The list of ion channel-affecting substances goes on: capsaicin, genistein, ginseng…ah, also omega 3 PUFAs and zinc. In fact, thanks to this study, genistein moved to the top of my to-be-tested supplement list.

My own ramblings. Okay, we know that very little curcumin ends up in the bloodstream, plus a lot of it gets transformed into metabolites that may not be as powerful as the original stuff (although that is an unresolved question, as we have seen in previous posts)…but just yesterday we learned that curcumin affects cell membranes…and today we find out that curcumin most likely affects ion channels, which are involved in cancer progression and metastasis. Well, the only possible conclusion, in my view, is that curcumin and other poorly bioavailable substances may work in ways that have yet to be explored. And this is all very encouraging to me, an enthusiastic curcumin-taker with smoldering myeloma…

Curcumin and cell membranes

Sherlock (grazie!) sent me the full curcumin/cell membrane study (abstract: http://tinyurl.com/atknp7), the one that I mentioned in my March 9 2009 post. What was I thinking? What do I know about gramicidin channels of varying lengths and bilayer deformations? Er, not much, I’m afraid…

But…I tried. And, incredibly!, I managed to glean a few pearls. As follows.

 

Despite intense interest in the physiological effects of curcumin, a general mechanism for its action has not been identified. Studies of curcumin have shown that it influences structurally unrelated membrane proteins across several signaling pathways.

 

So the business about curcumin possibly affecting membranes had been hypothesized in previous studies. In a moment of utter madness, I actually glanced at a couple. A 2008 study (see http://tinyurl.com/buza49) suggested that curcumin affects the function of membrane proteins. But these changes had not been studied in detail until Prof. Ramamoorthy and his group examined them with solid-state nuclear magnetic resonance techniques (see: http://tinyurl.com/cvvzb3).

 

After trying to make heads or tails of quadrupolar coupling, acyl chains, anionic amphiphiles and all the other incomprehensible (to me) thingies mentioned in Prof. Ramamoorthy’s report, I gave up and jumped directly to the Discussion…parts of it were beyond my comprehension even after several read-throughs. But a few things were fairly clear.

 

An interesting suggestion concerns liposomal curcumin: It has also been reported that liposome-encapsulated curcumin has greater bioavailability and in vivo efficiency. Our results suggest that the incorporation of curcumin into liposomes strongly enhances the stability of curcumin and may have a strong impact on the demonstrated greater effectiveness of liposomal curcumin.

 

Curcumin stuck inside a liposome (see: http://en.wikipedia.org/wiki/Liposome)….a simple (?) solution that sounds better (to me) than the enteric-coated capsule idea.

 

Important excerpt: Cancer cells treated with curcumin display some features typical of apoptotic cell death […]. However, other features of curcumin-induced cytoxicity […] are not typical of standard apoptosis and point to a direct action of curcumin on the membrane as the initial step in the cytotoxic effect of curcumin on cancer cells. Fascinating.  

 

In conclusion, this 2009 study is the first to detail the real and dramatic changes caused by curcumin in cell membranes. I found most of it difficult or even impossible to interpret, but the parts that suggest that curcumin’s anticancer activity begins at the atomic level might help explain why this yellow-orange powder keeps some of us stable in spite of its well-documented poor bioavailability. Of course, given my lack of scientific training, this is just my own guesswork!

Oats and IL-1 beta

Occasionally I come across more substances that inhibit, or may inhibit!, IL-1 beta, which is a key SMM-MM progression factor (see my page on IL-1 beta or my early February posts). Just the other day I found another one: oats! Or, more precisely, polyphenols from oats called avenanthramides. A 2008 study on the prevention of atherosclerosis (see: http://tinyurl.com/croz5k) tested human aortic endothelial cells with the purpose of determining if the mechanism of inhibitory effect of these polyphenols from oats on the expression of proinflammatory cytokines is mediated through modulation of nuclear factor-kB-dependent transcription.

 

This study (grazie, Sherlock!) mainly examines a synthetic form of avenanthramides called CH3-Avn-c, which, to be honest, is of little interest to me (ALL I need is another pill or capsule, argh!). I am more interested in the following:

 

Taken together, our results demonstrate that Avns, specific polyphenols from oats, possess potential anti-inflammatory properties, which may lend to their potential beneficial effect in the prevention of atherosclerosis through inhibition of NF-kB activation. It is interesting to note that oatmeal bath has been used for skin conditions such as eczema, poison ivy, insect bites, sunburn, and shingles, where inflammation is known to be the main culprit. Our findings are in line with the observation of several naturally occurring polyphenols in foods, spices, and herbs, such as curcumin, myricetin, quercetin, resveratrol, and green tea constituent (–)-epigallocatechin-3-gallate (EGCG), all of which have been suggested to have health benefit effects through long-term consumption by modulating NF-kB activity.

 

Long-term. Hmmm. This adjective is a good reminder that there are no quick fixes with natural extracts. Patience is key. If something doesn’t work immediately, perhaps we shouldn’t discard it right off the bat. Well, unless our markers worsen, of course. That’s a different story…

 

Another important excerpt: Our data also point to the potential benefit of including oats and oat bran in daily meals over the long term. Oat products not only are known to reduce blood cholesterol, but also may help to suppress the inflammatory process associated with the development of atherosclerosis. “Long term” is mentioned again in this paragraph. Eh. We are also reminded that oats have a beneficial effect on blood pressure and are a rich source of many nutrients and antioxidants including vitamin E, phytic acid, and unique polyphenols, avenanthramides.

 

Well, including oats in our diet may not do much to inhibit IL-1 beta in the short term (no quick fixes!), but they are good for us in so many other ways. I am going to eat more (organic) oats from now on. In fact, I just had a bowl of (organic) oatmeal and flaxseed for lunch!

 

My motto of the week: can’t hurt…could help!

Gracious hostility and electric girdles…

A blog reader sent me this list. Enjoy!

 

Church Bulletins

 

The following items actually appeared in church bulletins or were announced in church services:

 

The Fasting and Prayer Conference includes meals.

 

The sermon this morning: “Jesus Walks on the Water.” The sermon tonight: “Searching for Jesus.”

 

Our youth basketball team is back in action Wednesday at 8 PM in the recreation hall. Come out and watch us kill Christ the King.

 

Ladies, don’t forget the rummage sale. It’s a chance to get rid of those things not worth keeping around the house. Bring your husbands.

 

The peacemaking meeting scheduled for today has been canceled due to a conflict.

 

Remember in prayer the many who are sick of our community. Smile at someone who is hard to love. Say “Hell” to someone who doesn’t care much about you.

 

Don’t let worry kill you off–let the Church help.

 

Miss Charlene Mason sang “I will not pass this way again,” giving obvious pleasure to the congregation.

 

For those of you who have children and don’t know it, we have a nursery downstairs.

 

Next Thursday there will be tryouts for the choir. They need all the help they can get.

 

The Rector will preach his farewell message after which the choir will sing “Break Forth Into Joy.”

 

Irving Benson and Jessie Carter were married on October 24 in the church. So ends a friendship that began in their school days.

 

A bean supper will be held on Tuesday evening in the church hall. Music will follow.

 

At the evening service tonight, the sermon topic will be What Is Hell? Come early and listen to our choir practice.

 

Eight new choir robes are currently needed due to the addition of several new members and to the deterioration of some older ones.

 

Scouts are saving aluminum cans, bottles, and other items to be recycled. Proceeds will be used to cripple children.

 

Please place your donation in the envelope along with the deceased person you want remembered.

 

The church will host an evening of fine dining, super entertainment, and gracious hostility.

 

Potluck supper Sunday at 5:00 PM–prayer and medication to follow.

 

The ladies of the Church have cast off clothing of every kind. They may be seen in the basement on Friday afternoon.

 

This evening at 7 PM there will be a hymn singing in the park across from the Church. Bring a blanket and come prepared to sin.

 

Ladies Bible Study will be held Thursday morning at 10 AM. All ladies are invited to lunch in the Fellowship Hall after the B. S. is done.

 

The pastor would appreciate it if the ladies of the congregation would lend him their electric girdles for the pancake breakfast next Sunday.

 

Low Self-Esteem Support Group will meet Thursday at 7 PM. Please use the back door.

 

The eighth-graders will be presenting Shakespeare’s Hamlet in the Church basement Friday at 7 PM. The congregation is invited to attend this tragedy.

 

Weight Watchers will meet at 7 PM at the First Presbyterian Church. Please use large double door at the side entrance.

 

The Associate Minister unveiled the church’s new tithing campaign slogan last Sunday: I Upped My Pledge–Up Yours.

Another curcumin myeloma clinical trial

Well, well, I just happened upon a lovely bit of news. Are you ready?

 

The MD Anderson curcumin myeloma clinical trial is not THE only one. Yep, that’s right. Another trial is being held right now in Australia. Well, okay, technically, it’s a MGUS, not MM, curcumin trial, as we will see in a second.

 

Let’s see, you can access the PDF file that provides some information about the trial (an interesting read, by the way), but for some reason it doesn’t seem to work unless you do a Google search (for instance, the words curcumin myeloma clinical trial Australia should bring up the correct Dove Press article).

 

OR you can click on this HTML link: http://tinyurl.com/crkjy3. Then click on the PDF link at the top of that page. You can then download the PDF file onto your computer.

 

OR (!) you can do another Google search for the title of the study “The potential role of curcumin (diferuloylmethane) in plasma cell dyscrasias/paraproteinemia.” I’m very sorry that I cannot provide a direct link (as I said, it doesn’t work, not for me anyway). But this search operation will take only a few extra seconds of your time.

 

If you don’t want to go to the trouble, though, then just read the following synopsis. The abstract tells us that Preliminary results from our pilot study show a drop of between 5% and 30% serum paraprotein in patients taking curcumin compared with patients on placebo. Thirty percent??? Holy cats and dogs! That’s Giovanni Allevi music to my ears…sweet!

 

The Australian researchers favour early intervention in MGUS patients to reduce the paraprotein load. I am in favour of that, too, but only if said intervention is made with non-toxic natural extracts. As in this case.

 

Toward the end of the article, we get to the relevant part: We are conducting a single blind randomized controlled pilot study on 25 patients with paraproteinemia. Entry criteria included patients defined as having MGUS ie, the presence of a serum paraprotein (greater than 8 g/L and less than 40 g/L) with the exclusion of multiple myeloma. These patients are being monitored for a 6 month period of curcumin or placebo therapy.

 

I almost got teary when I read what followed: Curcumin or placebo is being administered orally as a 2 grams twice daily regimen. After one week on curcumin, there has been a drop of between 5% and 30% serum paraprotein in some patients, compared to controls […]. After 3 months of curcumin therapy, these reduced levels have remained suppressed. These exciting findings have prompted a double-blind, randomized, controlled trial. The benefits of the fall in paraprotein is uncertain. How long these reduced levels will remain suppressed and what the clinical benefits are, remain to be seen. As a natural product, it has exciting potential in the treatment of plasma cell dyscrasias. Only TWO grams of curcumin??? YAY!!!

I say, this is very exciting news indeed. Another trial! Plus, the preliminary results are bloody excellent. Hoppity hop! Needless to say, I have a million questions that I hope will be answered soon. For instance, I wonder what type of curcumin these patients are taking, how they are taking it, blablabla. Rest assured, as soon as I have any news, I will post it. Good or bad, as always…but hey, how could it not be good?!!!

Bathroom humour…

Yesterday a blog reader/friend (thanks!) sent me a funny e-mail. I forwarded it to family and friends, but decided that I had to post about it, too, even though I had planned to post on a more serious topic today. bathroom-floorWell, “serious” can wait until tomorrow…besides, er, this could be seen as a continuation of yesterday’s “bathroom” post….okay, here goes…

 

 

 

First image. Imagine that you are at a party. On the 10th floor of a high-rise building.

 

And then you have to pay a visit to the bathroom…

 

You open the door….

 

And find….THIS.

 

It’s just a painted floor,public-toilet-1 of course, but doesn’t it make you wonder if you would have the guts to step inside this high-rise bathroom?

 

 

 

 

 

Sepublic-toilet-2cond and third image.

 

This woman is getting ready to enter a public toilet in Houston, Texas.

 

Okay, you’ve seen the outside (above, on the right), now check out…the inside (on the left)…

 

It’s made entirely of one-way glass. Nobody can see you from the outside, but when you are inside, it’s like sitting inside a clear glass box.

 

Now…truthfully…would you…indeed, COULD you…???