Throughout the years, I have bought my cats what I have considered to be fantastically fun cat toys. “They’re going to love THIS one,” I would stubbornly repeat to myself. Well, “this one” usually joined the other discarded toys in a basket. I guess my idea of “great cat toy” doesn’t coincide with theirs. But even though I now almost never buy any cat toys (empty cardboard boxes are much more fun, you see), I do occasionally fall for a new, uhm, “great” toy.

 

My cats’ initial reaction is usually satisfactory. They will look at it, sniff it and even pretend to be interested for a moment or two. If I’m lucky, they will politely bat it around the room for a few seconds. Then they will look at me disdainfully, as though saying “is that IT? Well, phooey to you, you foolish tall creature,” and strut off, with their tails straight up in the air.

 

But there is one toy that has managed to keep my kitties’ interest alive. It’s a dumb little thing, really, something that you could easily make yourself: a small flat piece of leather shaped like a squished mouse (the shape, I suppose, is intended for us dumb humans; I’m sure cats wouldn’t notice if it were the outline of an elephant or a ladybug) and stuck on the end of a piece of string. I call it “mousie.” All of my cats have loved and enjoyed playing with mousie.

 

Peekaboo, my youngest kitty is no exception. She goes absolutely bonkers over mousie. At night, Peekaboo and I frequently play with mousie until I have had enough. At that point, I distract her somehow (not easy), then, unbeknownst to her or hah so I think!, I hastily shove mousie inside my pyjama pocket and try to look nonchalant. She usually spends a few minutes frantically hunting for mousie all over us and our bedroom but finally gives up and settles down in my lap. As soon as I get the chance, I sneak out of bed, slink over to the bathroom, lock myself inside and hide mousie on top of the bathroom cabinet. Out of sight. Phew. There is NO way Peekaboo can figure out where mousie is. Right?

 

Wrong.

 

For the past week or so, I have not had one single peaceful, er, session in the bathroom, not even to clean out the litter box. As soon as I shut the door, Peekaboo throws herself forcefully against it. She is actually able to open it (if it’s unlocked). When she cannot get in, though, she scratches frantically at the door and howls piteously…a hyena being slowly and painfully strangled could not possibly emit a more horrible noise…I am convinced my next door neighbours think that we torture our cats in atrocious ways…

 

At first, I just couldn’t figure it out. She’d never before been interested in the bathroom. Besides, she doesn’t howl in front of the bathroom door when Stefano is inside, so what is her problem with MY being in there? I imagined it could possibly be a form of “separation anxiety.” Yes, I even got a bit emotional at the thought that my sweet little baby just couldn’t stand losing sight of her mommy and felt the need to be with me every instant of the day. Oh, I know, I know…

 

Then a faint light went on in my brain. Point 1: She must somehow have found out that mousie is inside the bathroom (and no, it is not a catnip toy). Point 2: I am always the one who plays mousie with her, not Stefano…so that is why she doesn’t care one whit about HIS being in the bathroom. Mystery solved.

 

But it gets worse. The cunning little creature is now trying to work out how to jump from the toilet to the top of mousie’s cabinet. Yesterday I caught her stretching her body upwards as far as she could, as if measuring the distance. When I walked into the bathroom, though, my petite drama queen threw herself on the floor, showing me her fuzzy little tummy and chirping seductively…as though not interested in anything but me…

 

Okay, clearly, it was time to change hiding places. Ah, no, wait, I had a better idea. Last night I put mousie on a bookshelf in my study, way up high, out of a cat’s reach, but making sure that Peekaboo had seen where it was. Will my kitty’s Sarah Bernhardt performances finally come to an end?

 

Hmmm, I doubt it. She has already let me know that she is on to me, that she is perfectly aware that mousie isn’t REALLY on my study bookshelf. “It’s still in the bathroom,” she informed me this morning with an affronted look. (But it’s not, it’s in my study, I swear!)

 

My (bathroom) peace has probably vanished…forever.

Hehe, I love it. Curcumin, the disciplinarian! According to yesterday’s Science Daily newsletter (see http://tinyurl.com/cgxhcp), a recent study shows how curcumin actually works inside the body, at the cell membrane level. Extraordinary. Curcumin actually gets inside our cell membranes, making them more orderly, thus improving the cells’ resistance to infection and malignancy. It acts like a disciplinarian: “behave or else…!!!”

 

My favourite quote from the article: The [cell] membrane goes from being crazy and floppy to being more disciplined and ordered, so that information flow through it can be controlled […]. Amazing, huh? 

 

Interesting titbit: the lead scientist in this project, Prof. Ramamoorthy, As a child in India, […] was given turmeric-laced milk to drink when he had a cold, and […] breathed steam infused with turmeric to relieve congestion.

 

I asked Sherlock if she could get her hands on the full study, but a quick glance at the abstract (http://tinyurl.com/atknp7) tells me that it may be way over my head. I will give it a whirl, though. One important excerpt from the abstract: curcumin has a strong effect on membrane structure at low concentrations. At low concentrations…hmmm, this might help explain a few things…

My cousin sent me the link to this video…I laughed out loud…had to share: http://tinyurl.com/djvk2d

Holy cats! I just read a rather unsettling Science Daily article (see: http://tinyurl.com/au9kzb). A new study shows that angiogenesis-inhibiting drugs may turn a blissful “well-fed” cancer into an angry aggressive type.

 

A group of U.S. and Spanish researchers found that mice first infected with pancreatic cancer and glioblastoma and then treated with the anti-angiogenic drug sunitinib responded rather well in the beginning…but, after a few weeks, there was an adaptive response by the tumor. The glioblastomas increased invasion into adjacent normal tissue. The pancreatic tumors also became more invasive and, in addition, metastasized to the liver.

 

This study suggests that tumours have a remarkable ability to develop survival strategies. If their blood supply is cut off, they will find other ways to feed themselves and survive…apparently, by spreading and becoming more dangerous. A scary thought indeed.

This article led me to reflect, once again, on the use of aggressive treatments versus gentler, less invasive ones…

A blog reader (thanks!) sent me the link to a food-for-thought 2003 Swedish study (see http://tinyurl.com/d4qc38) on nicotinamide, a water-soluble member of the vitamin B family (specifically, the amide derivative of vitamin B3).

 

Now, this study doesn’t examine myeloma but is still relevant to us because it shows that nicotinamide inhibits IL-1 beta (=SMM-MM progression factor), IL-6 and TNF-alpha by, tadaaa!, 95%. I repeat, by 95%. And it also inhibits IL-8, an angiogenesis cytokine in myeloma, by 85%. This is all most intriguing.

 

This was an in vitro experiment, conducted on healthy human blood incubated with endotoxin, which stimulated the response of the above-mentioned cytokines. Nicotinamide, when added to the mix, inhibited all four cytokines, which is great news. The researchers conclude: As the proinflammatory cytokine response of IL-1beta, IL-6, IL-8 and TNFalpha following endotoxin stimulation of human whole blood is profoundly inhibited by nicotinamide, nicotinamide may have a therapeutic potential as a modulator of cytokine effects in inflammatory disease. Super duper!

 

Now, the study kept mentioning this thing called PARP…no idea what that was, so I had to look it up. The acronym stands for “polyadenosine-5′-diphosphate-ribose polymerase.” Uhm. Okay, spelling it out doesn’t help matters. Forget the acronym.

 

Let’s see (flip flip flip…flipping virtual pages)…ah, here we go: PARP is basically a protein linked to DNA repair, cell proliferation and apoptosis. Interesting factoid: NF-kappaB cannot be activated unless PARP is also activated, as we can see by glancing at this 1999 abstract: http://tinyurl.com/b8hmsc.

 

And, of course, PARP is involved, not in a good way, in myeloma. Hah!

 

A 2005 abstract (http://tinyurl.com/dkyk39) tells us, in fact, that the outcome of PARP cleavage is the apoptosis (=programmed cell death) of myeloma cells. PARP whaaat??? Oh, okay, simply put, PARP cleavage has nothing to do with embarrassingly low necklines but is a typical manifestation of apoptosis. Basically, anything that induces PARP cleavage in myeloma (or any type of cancer) cells is a good…anything.

 

So…my next step was to check out PARP cleavage and curcumin. Well, quelle surprise!, curcumin induces PARP cleavage in myeloma cells (see, e.g., the 2003 MD Anderson curcumin-myeloma study to which I link from my blog): Suppression of NF-kB by curcumin also led to apoptosis of MM cells, as indicated by activation of caspases and cleavage of PARP. So this cleavage business is one of the ways that curcumin annihilates myeloma cells. Good to know.

 

I took this all a bit further. Not surprisingly, parthenolide also induces PARP cleavage in myeloma cells (see: http://tinyurl.com/bdbqzj): Parthenolide rapidly induced caspase activation and cleavage of PARP […]. Capital, capital.

 

Other substances that induce this important cleavage process (perhaps not specifically in myeloma, though; I would need more time to check that out) are:

DHA (omega-3), see: http://tinyurl.com/d4eje2

Quercetin: http://tinyurl.com/cusjx9

Resveratrol: http://tinyurl.com/alfd25

Capsaicin: http://tinyurl.com/dn325k

 

Okay, enough, enough, I don’t have the time to go down the list of supplements on my blog. But anyway, wanna bet that most if not all induce PARP cleavage in some type of cancer?

 

As soon as I finished reading the nicotinamide study, I went downstairs and took my vitamin B supplement (a gooey but tasty liquid with other things in it, too). I take it only now and again, when I need an energy boost…but perhaps now I will begin taking it more frequently. Hey, you never know…

 

Quick consideration. Funny how we tend to overlook things that we don’t understand or don’t think are important. Selective memory, eh? You see, I don’t remember any mention of PARP cleavage in the MD Anderson 2003 curcumin study, a study that changed my life. Yet PARP is mentioned in that study as many as 15 times (I just counted ’em)! But all that mattered to me back then was that curcumin killed myeloma cells. How this actually occurred was not important. Now, though, after three years of research, I am a bit more interested in understanding the mechanics of these apoptotic processes. Not easy…for an unscientific mind…like mine. Oh, how I wish I had a photographic memory!

 

Fascinating bit of news. According to a Science Daily article (http://tinyurl.com/bbvgc3), a study, published in February in the journal “Sleep,” shows a link between sleep duration and the production of cytokines…mainly, IL-6 and C-reactive protein or CRP. Okay, that really caught my attention, since both are involved up to their ears in myeloma progression.

 

Let’s take a quick look. Each additional hour of self-reported sleep duration was associated with an eight-percent increase in C-reactive protein (CRP) levels and a seven-percent increase in interleukin-6 (IL-6), which are two inflammatory mediators. In contrast, each hour of reduction in sleep measured objectively by polysomnography was associated with an eight-percent increase in tumor necrosis factor alpha, another pro-inflammatory cytokine.

 

So if we don’t go to sleep at all, our CRP and IL-6 levels will go way down (good), but at the same time our TNF alpha levels will go up (bad, but I am more concerned about IL-6 and CRP in myeloma). Hmmm. Okay, I am now seriously thinking about sleeping less…no, no, wait, there is some bad news…the less we sleep, the more we increase our chances of developing diabetes, hypertension and obstructive sleep apnea. Oh, phooey! Uffa! And there is more…

 

Another Science Daily article (see http://tinyurl.com/cclaml), published last fall, tells us that loss of sleep can prompt one’s immune system to turn against healthy tissue and organs. Er, not sure I like the sound of that…In fact, we have a better chance of avoiding heart and autoimmune diseases if we get a good night’s sleep. And, incidentally, the researchers in this particular study measured our old friend, NF-kappaB., which turned out to be higher in women who were sleep-deprived. Hah. And more…

 

A related issue. According to HealthDay (http://tinyurl.com/9cvhl6), our immune systems work better at night: Stanford University research with fruit flies reveals that the immune system fights invading bacteria the hardest at night and the least during the day. Stanford University researchers found that fruit flies, whose genetic makeup is incredibly similar to ours, were better able to fight bacterial infections at night than during the day. Well, this would seem to support one of my gut feelings: that it is better to take curcumin and other supplements late in the day, when the body’s metabolism slows down.

 

Just for the heck of it, I looked up sleep and immune function on PubMed, where I found loads of studies. This 2009 one (full study: http://tinyurl.com/ard2yd), for instance, tells us that Species that have evolved longer sleep durations appear to be able to increase investment in their immune systems and be better protected from parasites. Indeed, further on the researchers suggest that sleep fuels the immune system and say that antibody responses and natural killer cell activity are reduced following sleep deprivation. And, in the Discussion part: Our results suggest mammalian species that spend more time asleep are able to increase investment in their immune systems, and thus are better protected from parasitic infection. Well, that explains why I slept almost all the time when I had pleurisy a couple of years ago, and why we sleep more when we have any sort of infection…interesting!

 

In conclusion. More sleep = higher CRP and IL-6 (bad) BUT also higher immunity and less susceptibility to heart/autoimmune diseases (good). Less sleep = lower TNF alpha (good) BUT higher NF-kappaB (only in women, though), lower immunity and increased susceptibility to diabetes, hypertension, sleep apnea, parasitic infections and heart trouble (bad bad bad).

 

Let’s see…hey, isn’t it about time for my nap/pisolino now??? (hehe)

Yesterday Stefano and I went to Siena, to an art exhibit examining the link between madness and art, mental disorders and creativity. The title states it clearly: “Art, Genius, Folly.” We saw works by Van Gogh, Edvard Munch, Antonio Ligabue and many others…a total of 400 paintings and sculptures from the past three centuries. One that struck my fancy was a curious painting attributed to Hieronymus Bosch, the “Concert in the Egg.” (see here: http://tinyurl.com/ap95qn). Overall, an interesting exhibit, at times a bit distressing, especially the initial part, devoted to how mentally disturbed patients have been treated throughout the centuries, beginning in the Middle Ages.

 

The art exhibit’s official website (in Italian): http://www.artegeniofollia.it/

News in English: http://tinyurl.com/c3kjrh

 

Afterwards, we walked around Siena and spent time photographing my favourite piazza in the world, Piazza del Campo. It was a beautiful day, and, by noon, also quite warm, about 15° Centigrade. The piazza was half-filled with people sunning themselves, sitting or lying down on the red-brick shell-shaped slope, reading a newspaper or a book. Little kids chasing after pidgeons. Families picnicking. It was so relaxing.

 

On our way back to Florence, we stopped in Monteriggioni, a fortified Medieval hilltop village in the province of Siena, built in the 13^th century. Monteriggioni (my new blog banner, by the way, is from a photo I took from a distance of this town’s circular walls) is extremely well-preserved and has not undergone any significant changes throughout the centuries. Thanks to Monteriggioni’s fortified walls and strategic position, its inhabitants were able to resist many attacks by the Florentines during the Middle Ages. My first photo of Monteriggioni (above) is taken just outside one of the town gates. The others (below) are inside views. 

 

From Wikipedia I learned that the Italian poet Dante Alighieri used the towers of Monteriggioni “to evoke the sight of the ring of giants encircling the Infernal abyss”:

 

‘però che, come su la cerchia tonda

Montereggion di torri si corona,

così la proda che ‘l pozzo circonda

torreggiavan di mezza la persona

li orribili giganti, cui minaccia

Giove del cielo ancora quando tuona.’

-Dante Alighieri, Inferno, Canto XXXI, lines 40-45

 

‘As with circling round

Of turrets, Montereggion crowns his walls;

E’en thus the shore, encompassing the abyss,

Was turreted with giants, half their length

Uprearing, horrible, whom Jove from heaven

Yet threatens, when his muttering thunder rolls.’

-as translated by Henry Francis Cary during the years 1805–1844

 

Final note: this is a sad period for some myeloma list members/bloggers. Teresa’s husband (see The Beast) just passed away. My heart goes out to her and her family. Another distressing item: a friend’s husband, a myeloma patient, is in the hospital, fighting for his life, after catching some sort of resistant bug and coming down with double pneumonia. Well, I hope to have some good news soon.

 

And this brings me to the following. Some blog readers have asked me about my “feverfew” blood tests. Well, I haven’t had any tests since November 2008. And, since the flu season is still going strong here, I have decided that I cannot and will not risk going up to the hospital lab for blood tests right now. I have postponed having tests done until the end of this month, at least. My feverfew experiment has lasted longer than predicted, unfortunately. But…better be safe than sorry!