1 Eylül 2013 Pazar

Lipoproteins & apolipoproteins: E, by 'eck.

In December 2008, I wrote about Cholesterol And Coronary Heart Disease , where I used a limousine metaphor to describe how cholesterol & fat are transported around the body. Here's a diagram of a chylomicron lipoprotein "limousine". Chylomicrons transport dietary fat (triglycerides) & cholesterol from the gut to the liver & other tissues. As there's much more dietary fat than dietary cholesterol, the contents are mostly fat.
A chylomicron. T=Triglyceride C=Cholesterol. From http://en.wikipedia.org/wiki/Lipoprotein

The lipoprotein "limousines" vary a lot in size.
(a) VLDL (b) chylomicrons (c) LDL (d) HDL. 
From http://healthcorrelator.blogspot.co.uk/2011/11/triglycerides-vldl-and-industrial.html

Apolipoproteins are the "chauffeurs" which determine to where lipoproteins transport stuff.
Apo A is found mainly on HDL, which transports fat & cholesterol from tissues to the liver.
Apo B is found mainly on LDL, which transports cholesterol from the liver to tissues.
Apo C is found on HDL when fasted, but moves to chylomicrons & VLDL when fat is eaten.
Apo D is found mainly on HDL and is is associated with an enzyme involved in lipoprotein metabolism.
Apo E is found mainly on chylomicrons & IDL and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and into the blood. In the CNS, Apo E transports cholesterol to neurons. Defects in Apo E result in hyperlipidaemia , cardiovascular & neurological diseases, and is the E referred to in the title.

There's also Apo H, which is a β-glycoprotein involved in the binding of cardiolipin. It has nothing to do with the above lipoproteins.

28 Ağustos 2013 Çarşamba

Things that make you go "Struth!"

I was wading through my Facebook News Feed when I spotted THIS. That article led me to New approach to coeliac testing identifies more Australians at risk, which in turn led me to A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways (provisional pdf), where I saw: "HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts."
HLA-DQ2.5, DQ8 & DQ2.2 are the alleles for Coeliac/Celiac Disease (CD).
Image from http://www.clker.com/clipart-tango-face-surprise.html
"Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLADQ2.5, DQ8, or DQ2.2."
There were abnormalities in ~5% of Australian women & ~7% of Australian men, even in those who didn't carry CD alleles.

"...but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men."
~1.6% of Australian women & ~1.3% of Australian men have CD.

From the discussion: "The concept of a ‘celiac iceberg’ has been important in drawing attention to a large, unrecognized group of patients with CD who do report symptoms considered ‘typical’ of CD [29]. Investigators have proposed expansion of the ‘iceberg’ to encompass patients who are genetically susceptible to CD, but show only raised IEL counts or an isolated abnormal CDspecific serology and normal intestinal histology [30-32]. Consequently, there is considerable uncertainty regarding the true extent of gluten-mediated disease in the community.

Random thoughts: About 1 in 20 Australian women & about 1 in 15 Australian men have some kind of a gut problem (IBS?) due to gliadin, even in those who don't carry CD alleles. The following made me smile.
"Making a diagnosis based on a blood test alone or commencing a gluten-free diet without a confirmatory bowel biopsy is inappropriate and can impose an unnecessary and lifelong treatment."
'Cos life without wheat, rye, barley & oats is such an imposition (undue burden) and everyone just loves to be given a bowel biopsy. <- sarcasm alert.

From Ancestry of Australian population: "More than 92 percent of all Australians descend from Europeans. Anglo-Celtic Australians (English, Scottish, Welsh, Cornish or Irish ancestral origin) make up 74 percent of the Australian population."
Most Australians have genes that originate from Britain & Europe. Uh-oh!

Why do only a small percentage of people carrying the CD allele go on to develop CD? I believe that it's down to luck. During digestion, gliadins are snipped into fragments & amino acids by the peptidase enzymes pepsin, trypsin & chymotrypsin. Gliadin fragments that contain the wrong triplet of amino acids and that manage to slip through excessively-loose tight junctions may trigger CD. Once the "damage is done", it only takes a tiny amount of gliadin to provoke an immune response.

26 Ağustos 2013 Pazartesi

False dichotomies: serum cholesterol level vs all-cause mortality. Cause or effect?

Here are some plots from the MRFIT study.
From http://sph.bu.edu/otlt/MPH-Modules/PH/PH709_Heart/PH709_Heart5.html

Although the relative risk (RR) for coronary heart disease (CHD) and cardiovascular disease (CVD) mortalities increase with serum total cholesterol (TC) level, all-cause mortality follows a U-curve.

According to Low Serum Cholesterol and Mortality: Which Is the Cause and Which Is the Effect?, certain illnesses that increase mortality lower TC levels. This is the Iribarren hypothesis.

According to Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study, TC that's low and is still low 20 years later results in a 64% increase in the RR for mortality relative to TC that's intermediate and is still intermediate 20 years later.

Table 4 Relative risk for mortality based on change in cholesterol between examinations three and four
Is low TC level the cause of, or the effect of fatal illnesses? I think that it's both. Cholesterol is an important substance, as a severe lack of it is bad news, as per Smith–Lemli–Opitz syndrome. If certain illnesses result in a depletion of cholesterol and cholesterol synthesis is too low, there's insufficient cholesterol to allow recovery.

Interestingly, TC that's low but is intermediate 20 years later results in a 30% increase in the RR for mortality, whereas TC that's low but is high 20 years later results in a 5% increase in the RR for mortality.

P.S. There's a false dichotomy for vitamin D level vs illness. Ditto for carbohydrates vs calories.

24 Ağustos 2013 Cumartesi

Molested milk: there's more to it than bovine xanthine oxidase.

The idea for the title came from Molested fats, Op. 139. Thank you, Bill!
Image from http://suppversity.blogspot.co.uk/2012/08/mutant-milk-new-research-fuels-flames.html

Homogenising/homogenizing milk has certain advantages, as per Creaming and homogenization.
"No link has been found between atherosclerosis and milk consumption." Hurrah! Not so fast...

According to Mutant Milk!? New Research Fuels the Flames on Hushed Up Concerns About Ill Health Effects of Homogenized Milk, homogenised milk has a different effect in the body (and not in a good way, if you're over-fat) from non-homogenised milk.
"...mice who received the regular formula with small lipid droplets were fatter and had compromised lipid and blood glucose levels, as well as pathologically increased leptin levels." Yeah, mice.

I drink Tesco Finest Channel Island Milk (a.k.a. Gold Top Milk). It's "past your eyes" (by law, all shop-bought milk in the UK must be pasteurised) but unhomogenised milk from grass-fed (during the summer) cows. During the summer, the cream is much more yellow than during the winter. To distribute the fat throughout the milk, you have to shake the bottle. Does that smash the milk fat globules to buggery? I think not.

Raw (i.e. unpasteurised) milk is legal in the UK, but the nearest farm where I can buy it is Meadow Cottage Farm in Churt. I used to buy it from them at a Farmer's Market in Aldershot, but that closed.

EDIT: I just noticed something in Why Doesn’t Medical Care Get Better When Doctors Rest More? (hat-tip to Yoni Freedhoff).
"Take heart failure—the most common reason for admission to the hospital in the United States—and a problem that I, as a cardiologist, deal with often." In the US, heart failure is now more common than blocked coronary arteries. See Is Coenzyme Q10 a supplement or a drug? It all depends. Statins reduce Coenzyme Q10 synthesis. Just saying.

22 Ağustos 2013 Perşembe

R.I.P. HP Deskjet F380. Long Live HP Deskjet 3520.

Last year, I had a problem with my HP Deskjet F380, in HP Deskjet F380 Ink Cartridge Error. On Monday 19th August, it happened again. This time, I threw the baby out with the bathwater and bought a new HP Deskjet 3520 e-All-in-One printer/scanner/copier (the F380 was over 6 years old).
From http://www.shopping.hp.com/en_US/home-office/-/products/Printers/HP-Deskjet/CX056A

This product has mixed reviews - people either love it or they hate it.

My initial observations:- It makes a lot of whirring noises - I hope this doesn't mean that it's going to wear out quickly. I like the fact that it can do double-sided printing. I like the fact that the menu screen is easily readable, with the printer on the floor underneath a telephone table. I don't like the fact that I can no longer see a print preview when printing from Notepad. I will use WordPad from now on. I prefer to not use "fancy" word processors like Microsoft Works Word Processor or Microsoft Word for simple documents like lyric/chord sheets. I can control all functions from my lap-top. Although the product has wireless capability, I'm using a USB cable, as with the F380.

Having imported an existing lyric/chord sheet into WordPad, I've reduced all margins to 3mm, as the HP 3520 adds borders by default. I've also had to use bold face to make the text as easy to read in dim light (typical open mic night setting) as the old sheets.

16 Ağustos 2013 Cuma

False dichotomies: moderation.

Feel like you're walking a tightrope? I sang this at Open Mic night on Wednesday, including the orchestration!


There's another internet "punch-up" over moderation in what people eat. Apparently, there are only two options:-

Everything in moderation,
Image from http://www.deltadentalarblog.com/2013/07/ditch-the-junk-help-your-kids-eat-better/
or Nothing in moderation.

As always, it's a case of "It all depends". If, when you're at home, you keep raiding the chocolates from the box or sweets/candies from the tin and you don't want to, don't have them in the house. However, if when you're not at home, someone offers you a chocolate or a small sweet/candy, unless you're so desperate that you'll steal some more or go to a shop and buy some more, eat the chocolate or small sweet/candy. Five grams of sugar won't harm you, even if you're diabetic.

If you have Coeliac Disease and mustn't eat any significant gluten, moderation isn't an option. Ditto, if you have impaired gut integrity and you feel better avoiding gluten. If consuming stuff doesn't cause you medical problems or make you desperate to consume even more, moderation is fine.

EDIT: Sometimes, I ramble in a way that makes it hard for people to understand what I'm talking about. I've emphasised the word "Apparently", as this post is about a perceived false dichotomy (perceived by the "Nothing in moderation" group).

12 Ağustos 2013 Pazartesi

Protein reduces endurance (in mice), food processing vs food refining & Schrödinger.

I saw the following study via Twitter. Dietary protein decreases exercise endurance through rapamycin-sensitive suppression of muscle mitochondria.
Mmm, protein!
Hmmm! In mice, a high protein diet significantly decreased the amount of muscle mitochondria, the mitochondrial activity and the running distance at 50 weeks, although it increased muscle mass and grip power.

A mouse's natural diet is fruit or grain from plants, though mice will eat virtually anything, including Kevlar insulation on wiring. Fruit & grains aren't particularly high in protein, so it's quite possible that eating a sub-optimal diet results in sub-optimal health.

If the results do translate to humans, we have a choice between endurance, and muscle mass & strength in our old-age. I know which I would choose. You'll have to prise the proteins from my cold, dead fingers!

More from TwitterA Major Communication Challenge of Our Times: What on Earth Do We Say About Processed Foods? The word "refine/refined" doesn't appear in the above article. I don't have a problem with food processing. What I do have a problem with is food refining. Just after the Mid-Victorian period, it became fashionable to eat foods that had been stripped of "impurities". Goodbye essential co-factors. Hello, degenerative diseases.

Finally, today is the 126th anniversary of Erwin Schrödinger's birthday. I have only one comment:-
Blatantly stolen from http://memegenerator.co/instance/31138345
:-)