Friday, June 28, 2013

The perfect mixer for hypertension .

The perfect mixer for hypertension  .

Andre Willers
28 Jun 2013
Synopsis :
Beetroot juice with alcohol will lower blood pressure .
Discussion :
1.There are lots of systems that increase BP . See Appendices A  , B  ,  D  .
2.ANP (Atrial natriuretic peptide )
 But only one that decreases BP .  Produced mostly in the heart .See Appendix C
3.Most of the vascular damage is not done by alcohol , but by the hangover . See Appendix D
4.Beetroot juice is high in nitrates . See Appendix E. (Think nitroglycerin) .
5.The BP cocktail :
2 Tots of vodka or cane
3 Tots of Beetroot juice.
Top up with ice , soda/water
Quite tasty , actually . 

Watch vascular stress decrease .
Enough of these , and you won’t care , in any case .

Appendix A
Renin-aldosterone axis in ethanol intoxication and hangover.
Linkola J, Fyhrquist F, Nieminen MM, Weber TH, Tontti K.
The renin-aldosterone system was studied in human volunteers during ethanol intoxication and hangover. Plasma renin activity increased more than 100%, when 1.5 - 2.3 g ethanol per kg body weight was ingested over a three hour period. During hangover the increase even exceeded 200%. Plasma aldosterone concentration decreased during ethanol intoxication, but increased greatly during hangover. It is suggested that the stimulation of the renin-aldosterone axis during ethanol intoxication and hangover is due to dehydration and increased activity of the sympathetic nervous system.
PMID: 1261587 [PubMed - indexed for MEDLINE]
Appendix B

Basic Review: The Renin-Angiotensin-Aldosterone Axis

One of the coolest aspects of the renin-angiotensin-aldosterone system (RAAS) is that it involves multiple organ systems: the liver, lung, adrenal gland, kidney, and vasculature are all prominently involved. It never hurts to review basic physiologic principles, right? Listed are the three main components of the RAAS and their main mechanisms of action.

1. Renin is a peptide hormone secreted from the juxtaglomerular cells of the afferent arteriole in response to 3 main stimuli: (a) renal hypoperfusion, (b) decreased distal chloride delivery to the macula densa, and (c) increased sympathetic activity. Renin antagonists such as aliskiren are presently being tested as antihypertensive agenst with thus far promising results.

2. Angiotensinogen--which is synthesized and secreted from the liver--is cleaved by renin in the systemic circulation to form angiotensin I.

Angiotensin I is cleaved to form angiotensin II by angiotensin converting enzyme (ACE), which is found predominantly within lung endothelium. ACE-inhibitors, as their name implies, targets the ACE enzyme and is one of the most potent anti-hypertensives (and GFR-preserving) therapies available.

Angiotensin II has the following physiologic effects, which it carries out via binding to AT1 and AT2 receptors. Drugs which block the ability of angiotensin II to bind to its receptors ("angiotensin receptors blockers", or ARBs) make up another highly successful and renoprotective antihypertensive therapy. Angiotensin II binding to its receptors have the following major effects:

a) angiotensin II acts as a systemic vasoconstrictor.
b) angiotensin II causes renal efferent arterial vasoconstriction. Acutely, efferent vasoconstriction should increase GFR; however, over time the increased glomerular pressure leads to glomerular damage and, ultimately, renal injury.
c) angiotensin II increases secretion of aldosterone from the zona glomerulosa of adrenal cortex.

3. Aldosterone: in cortical collecting duct cells, aldosterone diffuses into the cell and interacts with the mineralocorticoid receptor, which upon binding translocates to the nucleus and increases expression of ENac. The end result of aldosterone action is sodium reabsorption and potassium & hydrogen secretion. In addition to angiotensin II, hyperkalemia can also stimulate aldosterone secretion. The drug spironolactone interferes with aldosterone interacting with its receptors, and can be effective in the treatment of hypertension.

Appendix C

Atrial natriuretic peptide
From Wikipedia, the free encyclopedia
For other uses, see ANP.
Natriuretic peptide A

Atrial natriuretic peptide (ANP), atrial natriuretic factor (ANF), atrial natriuretic hormone (ANH), Cardionatrine, Cardiodilatine (CDD) or atriopeptin, is a powerful vasodilator, and a protein (polypeptide) hormone secreted by heart muscle cells.[1][2][3] It is involved in the homeostatic control of body water, sodium, potassium and fat (adipose tissue). It is released by muscle cells in the upper chambers (atria) of the heart (atrial myocytes) in response to high blood pressure. ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure.[1] ANP has exactly the opposite function of the aldosterone secreted by the zona glomerulosa.[4]
The ANP gene has 3 exons and 2 introns; it codes 151-amino acid preproANP. Cleaving the 25-amino acid N-terminal results in pro-ANP. Corin, a membrane serine protease, cleaves the final ANP, the 28-amino acid C-terminal.
ANP is produced, stored, and released mainly by cardiac myocytes of the atria of the heart. Synthesis of ANP also takes place in the ventricles, brain, suprarenal glands, and renal glands. It is released in response to atrial stretch and a variety of other signals induced by hypervolemia, exercise, or caloric restriction.[1] The hormone is constitutively expressed in the ventricles in response to stress induced by increased afterload (e.g. increased ventricular pressure from aortic stenosis) or injury (e.g. myocardial infarction).
ANP is secreted in response to:
Atrial distention, stretching of the vessel walls[1]
Sympathetic stimulation of β-adrenoceptors
Raised sodium concentration (hypernatremia), though sodium concentration is not the direct stimulus for increased ANP secretion[1]
Endothelin, a potent vasoconstrictor
The atria become distended by high extracellular fluid and blood volume, and atrial fibrillation. Notably, ANP secretion increases in response to immersion of the body in water, which causes atrial stretch due to an altered distribution of intravascular fluid. ANP secretion in response to exercise has also been demonstrated in horses.[6]
ANP is also produced by the placenta in pregnant women. The exact function of this remains unclear. [7]

ANP binds to a specific set of receptors – ANP receptors. Receptor-agonist binding causes a reduction in blood volume and therefore a reduction in cardiac output and systemic blood pressure. Lipolysis is increased and renal sodium reabsorption is decreased. The overall effect of ANP on the body is to counter increases in blood pressure and volume caused by the renin-angiotensin system.
Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the mesangial cells. This increases pressure in the glomerular capillaries, thus increasing the glomerular filtration rate (GFR), resulting in greater excretion of sodium and water.
Increases blood flow through the vasa recta which will wash the solutes (NaCl and urea) out of the medullary interstitium.[10] The lower osmolarity of the medullary interstitium leads to less reabsorption of tubular fluid and increased excretion.
Decreases sodium reabsorption in the distal convoluted tubule (interaction with NCC)[11] and cortical collecting duct of the nephron via guanosine 3',5'-cyclic monophosphate (cGMP) dependent phosphorylation of ENaC
Inhibits renin secretion, thereby inhibiting the renin-angiotensin-aldosterone system.
Reduces aldosterone secretion by the adrenal cortex.
Atrial natriuretic peptide (ANP) increases Na+ excretion by decreasing the amount of Na+ reabsorbed from the inner medullary collecting duct via a decrease in the permeability of the apical membrane of the collecting duct epithelial cells. Less Na+ is able to enter the epithelial cells and therefore, less Na+ is reabsorbed. ANP also increases Na+ excretion by increasing the filtered load of Na+
Relaxes vascular smooth muscle in arterioles and venules by:
Membrane Receptor-mediated elevation of vascular smooth muscle cGMP
Inhibition of the effects of catecholamines
Inhibits maladaptive cardiac hypertrophy
Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly[12]
Re-expression of NPRA rescues the phenotype.
It may be associated with isolated atrial amyloidosis.[13]
Adipose tissue[edit]
Increases the release of free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR-A
Increases intracellular cGMP levels that induce the phosphorylation of a hormone-sensitive lipase and perilipin A via the activation of a cGMP-dependent protein kinase-I (cGK-I)
Does not modulate cAMP production or PKA activity

Regulation of the effects of ANP is achieved through gradual degradation of the peptide by the enzyme neutral endopeptidase (NEP). Recently, NEP inhibitors have been developed; however they have not yet been licensed. They may be clinically useful in treating congestive heart disease.
Other natriuretic factors[edit]

In addition to the mammalian natriuretic peptides (ANP, BNP, CNP), other natriuretic peptides with similar structure and properties have been isolated elsewhere in the animal kingdom. Tervonen (1998) described a salmon natriuretic peptide known as salmon cardiac peptide,[14] while dendroaspis natriuretic peptide (DNP) can be found in the venom of the green mamba, a species of African snake.[15]
Pharmacological modulation[edit]

Neutral endopeptidase (NEP) is the enzyme that metabolizes natriuretic peptides. Several inhibitors of NEP are currently being developed to treat disorders ranging from hypertension to heart failure. Most of them are dual inhibitors. Omapatrilat (dual inhibitor of NEP and angiotensin-converting enzyme) developed by BMS did not receive FDA approval due to angioedema safety concerns. Other dual inhibitors of NEP with ACE/angiotensin receptor are currently being developed by pharmaceutical companies.[16]
Appendix D

To study the mechanisms of alcohol-induced diuresis, the plasma concentration of immunoreactive atrial natriuretic peptide and arginine vasopressin, serum sodium and osmolality, plasma renin activity and aldosterone, urinary sodium and volume, free water clearance, blood pressure and heart rate were measured in seven healthy men after oral intake of ethanol (1.5 g kg-1 in 6 h). Serum ethanol levels increased to 27 ± 4 mmol 1-l (mean ± SD) in 30 min and remained detectable for 14 h. Serum osmolality rose from 280±10 to 340 ± 4 mosm kg-1 in 2 hours (P < 0.01) and was 300 ± 4 at 14 h (P < 0.01). Formation of hypotonic urine began after the alcohol intake and resulted in a net loss of 0.9 ± 0.1 kg water in 2 h. Free water clearance increased from -3.4 ± 1.4 to 2.8 ± 1.5ml min-l in 2 h (P < 0.01). Plasma immunoreactive arginine vasopressin decreased from 5.7 ± 2.1 to 3.3 ± 1.3 ng 1-1 (P = 0.05) in 30 min and increased to 17 ± 25 and 12±10 ng 1-1 at 6 and 12 h, respectively (P < 0.05 for both). Plasma immunoreactive atrial natriuretic peptide levels decreased from 17 ± 9 to the minimum of 11 ± 3 ng 1-1 in 2 h (P < 0.01) and returned to the initial levels in 6 h. Serum sodium, plasma renin activity and plasma aldosterone increased maximally by 4 ±2, 165 ± 153 and 143 ± 101 % (P < 0.01 each) during 1–6 h. No changes in blood pressure were observed during the ingestion period, but the heart rate rose significantly from 70 min-1 at 6 p.m. to 95 min-1 at 12 p.m.

We conclude that ethanol intake in relation to serum ethanol levels caused in the first phase a rapid increase in osmolality which was associated with a decrease in plasma immunoreactive arginine vasopressin. This caused hypotonic diuresis and increased free water clearance followed by volume contraction which evidently led to decreased plasma immunoreactive atrial natriuretic peptide. Serum osmolality was significantly elevated during the whole experiment and serum sodium 1–2 h after the ethanol intake. This was associated with the return of plasma immunoreactive atrial natriuretic peptide to initial levels after 6 h, the increase in plasma immunoreactive arginine vasopressin levels and reduced diuresis after 2 h. Our results suggest that ANP is not responsible for the diuresis seen after the alcohol intake.
Appendix E
Nitric Oxide Signalling in Vascular Control and Cardiovascular Risk

Annette Schmidt1
[1] Leibniz-Institute of Arteriosclerosis Research at the University of Muenster, Germany
1. Introduction

Nitric oxide – a free radical molecule – has been known for many decades, but only since its recognition as endothelium-derived relaxing factor (EDRF) the interest in the molecule has exponentially increased (Moncada, 1991). At the present time NO is an important messenger that regulates numerous functions and also participates in the pathogenesis of various diseases (Lloyd-Jones & Block, 1996). NO is generated from the conversion of arginine to citrulline in a multistep oxidation process by the NO-synthase (NOS), a NADPH-dependent enzyme that requires Calcium-Calmodulin, Flavinadeninedinucleotide, Flavinmononcleotide and Tetrahydro-L-biopterin as cofactors (Förstermann et al., 1994). Three isoforms of NOS have been identified. All isoenzymes, the neuronal NOS (nNOS), the inducible NOS (iNOS) and the endothelial NOS (eNOS) (Liu & Huang, 2008), are homodimers with subunits of 130 – 160 kDa. As major signalling molecule of the vascular system NO is generated by the constitutively expressed eNOS.


Sunday, June 23, 2013

Tourettes and Parkinsons

Tourettes  and Parkinsons

Andre Willers
23 Jun 2013
“In vino veritas”
Synopsis :
Inability of intentions .

Discussion :
1.Parkinsons is the inability to perform intensions . (Movements ,Rls)
2.Tourettes is the inability to perform intensions .(Tics ,lies , RLS)
3.The same thing .
4.Cures for one will affect the other . Like  Pexola
5. Pexola enables performance of intentions for RLS . (Restless Leg Syndrome)
6. Pexola thus enhances creativity in pulsed dosages
7.Alcohol does something similar . The pulsation is built into the hangover .
8.Creative persons will be more likely to develop RLS and Parkinsons .
9.Intervention : Pexola and alcohol should be pulsed in a mutual inverse relationship .
10. Decrease pexola if you are drinking , and vice versa .
11.All to do with the dopamine system .
Simple enough .

Friday, June 21, 2013

The Digital Conscience .

The Digital Conscience

Andre Willers
21 Jun 2013
“Rebellion always starts among the angels”
Synopsis :
Digital artifice can and has erected a barrier between impulse and conscious decision .
Discussion :
1.The impulse decision
This arises from various deep brain layers and can be digitally detected before it surfaces in the conscious mind .
See Appendix A
We all know it .
But the conscious mind can override it .
Called will-power or conscience .
Now it can be done with a trainable digital system (AI=NeuralNet + Rules)
Coupled with lightweight sensors  (like ) or subdermal implants ,
an artificial conscience can be added .
2.Children :
This will work well with children , in the best Jesuitical fashion
3.Psychotics might need something more muscular than a “Stop” signal .
4.Peer pressure with muscle .
All the bullies you have known , loaded in your brain .
5.I wonder how long it will last ?
Not very long . The equivalent has been tried in history . Religions , Sparta , etc , etc .
“The fish rots from the head”

6.Hierarchies :
These control systems are all hierarchical .
Rebellion always starts among the angels .
7.Still , a very useful therapeutic and training tool .
8. Free will :
This will become a very pertinent question .
How much to control , and how much to allow through for optimization ?
9. You already know the answer .
1/3 should be Stop-blocked and 2/3 allowed freely , on a random basis for normals .
This is already the case with discipline systems .
1/3 is sufficient for socialization , and 2/3 for individualization .
10 Sicko’s
The ratio’s might have to be adjusted for them .
Interesting times , indeed .
Good will
Appendix A
Brain imaging spots our abstract choices before we do

16:46 10 April 2013 by Caroline Williams
For similar stories, visit the The Human Brain Topic Guide
When it comes to making decisions, it seems that the conscious mind is the last to know.

We already had evidence that it is possible to detect brain activity associated with movement before someone is aware of making a decision to move. Work presented this week at the British Neuroscience Association (BNA) conference in London not only extends it to abstract decisions, but suggests that it might even be possible to pre-emptively reverse a decision before a person realises they've made it.

In 2011, Gabriel Kreiman of Harvard University measured the activity of individual neurons in 12 people with epilepsy, using electrodes already implanted into their brain to help identify the source of their seizures. The volunteers took part in the "Libet" experiment, in which they press a button whenever they like and remember the position of a second hand on a clock at the moment of decision.

Kreiman discovered that electrical activity in the supplementary motor area, involved in initiating movement, and in the anterior cingulate cortex, which controls attention and motivation, appeared up to 5 seconds before a volunteer was aware of deciding to press the button (Neuron, This backed up earlier fMRI studies by John-Dylan Haynes of the Bernstein Center for Computational Neuroscience in Berlin, Germany, that had traced the origins of decisions to the prefrontal cortex a whopping 10 seconds before awareness (Nature Neuroscience,

"It's always nice when two lines of research converge and to know that what we see with fMRI is actually there in the neurons," says Haynes.

STOP sign for the brain

Kreiman told the BNA conference that he is now working on predicting decisions in real time, and to see if it is possible to reverse a decision before it hits consciousness – by flashing up the word "stop" on a screen as soon as telltale activity shows up in the brain.

There are no firm results yet, but Kreiman suspects there may be a measureable "point of no return" in the brain. "So far all we have is people saying, 'that was weird, you read my mind'," he says.

If this kind of "mind-reading" is possible, a new study by Haynes, published this week and also presented at the meeting, suggests that it may not be restricted to decisions about moving a finger. Using fMRI, Haynes has found that the very brain areas involved in deciding to move are also active several seconds before a more abstract decision, like whether to add or subtract a series of numbers.

He suggests that the prefrontal and parietal cortex may be general decision-making circuitry, passing activity on to different parts of the brain depending on the task at hand (PNAS, "Perhaps decisions arise from a similar set of areas, then either flow into motor systems, for pressing buttons, or the parietal cortex for doing calculations," he says.

Not hijacking the mind

Unless you happen to have electrodes inserted into your brain, there is no chance of decisions being hijacked by unscrupulous scientists, and Kreiman is keen to point out that he is not bent on world domination. "We're not trying to do mind control; we are trying to find out the mechanisms of volition," he says. "It might help people with Parkinson's disease, where people lose voluntary movement."

As for what it means for one of the longest-running debates in science – the question of whether we do or do not have free will – Haynes is pretty clear. "What we need now is 20 years of serious neuroscience, not more speculation about the handful of studies that have been done so far," he says.

Kreiman agrees, but says that these early results at least bring the question of free will out of the realms of magic and mystery. "There is no magic. There are neurons, and there are ions that flow through membranes, and that it what is orchestrating our decisions," he says. "We don't need to invoke freedom."


Easy Orbits .

Easy Orbits

Andre Willers
21 Jun 2013
Synopsis :
The Titius-Bode Law of orbital distances have been revamped and applied to discovered exo-planets . A good fit was found . An Intra-Mercurial is deduced .
Discussion :
An old discarded empirical “Law” has been picked up , dusted off , revamped and is now used to find Solar and exo-Solar planets .
The Intra-Mercurials can be seen in para 2 below .(0.188888 AU) . Possible shepherd planets .

1.A summation :
A handy guide to planetary parking spots

17 April 2013 by Jacob Aron
Magazine issue 2913. Subscribe and save
Read more: Click here to read the original, longer version of this story

NEED somewhere to park your planet? You won't have to circle the galaxy for long: up to two-thirds of planetary systems have empty spaces where an extra world could comfortably reside.

The gravitational tug-of-war between a star and its orbiting planets means that the worlds must be spaced at particular distances or else their orbits become unstable. The planets will then wobble around until some collide or are ejected.

Our current understanding of planetary formation suggests that most stable systems should be filled to capacity. "In the solar system, we know that's not quite true, because we know that in between Mars and Jupiter you could put another planet," says Sean Raymond at the Laboratory of Astrophysics of Bordeaux in France. Some theories say we started out with more worlds, but jostling with Jupiter caused some to be ejected 4 billion years ago.

Julia Fang and Jean-Luc Margot at the University of California, Los Angeles, wanted to find out whether other planetary systems are full, or if they also have unoccupied but stable orbital slots in between their planets.

The pair simulated millions of systems in a variety of orbital configurations and compared their models with real systems seen by NASA's Kepler space telescope. This told them which of their modelled systems are spaced right to be stable. The duo then checked whether these systems had orbital slots going spare, by sticking an extra planet in between two existing ones and modelling how the orbits evolved over 100 million years. Would it cause a collision or ejection?

Fang and Margot discovered that about a third of the stable two- and three-planet systems they modelled would go haywire if they added a world, rising to nearly half for four-planet systems (The Astrophysical Journal, That means the remaining majority of systems have empty stable zones, although that proportion could be revised downwards as more systems are discovered.

Pinning down spaces between known exoplanets might be useful for finding worlds that have so far avoided detection, says Raymond. "You can say, 'We think there should be a planet on this orbit, go look for it'," he says.

In fact, two other astronomers have found seemingly unoccupied slots that may in fact harbour potentially habitable worlds. Their method involves reviving the Titius-Bode relation, a rough mathematical rule for predicting planetary spacing. Developed in the late 1700s, the rule initially worked well for our solar system but fell out of favour when it conflicted with the discovery of Neptune in 1846.

Charles Lineweaver and Timothy Bovaird of the Australian National University in Canberra have now applied the equation to 64 other known systems that contain multiple planets or planet candidates. They found that it works as well as – or better than – it does for the solar system in 89 per cent of cases ( The rule also suggested unoccupied but stable orbital slots in several systems discovered by Kepler, including two in the life-friendly zone around the star KOI-490.

The team reckons these spaces contain as-yet-undetected planets. But if some systems have a truly empty slot, could a sufficiently advanced civilisation build a planet and park it in orbit? "Gravitationally it would certainly work out, I'm just not sure about the logistics," says Fang.

This article appeared in print under the headline "Handy guide shows planet parking slots"


2. Bit more detail
They predict a trans Plutonian called Eris .
But extrapolating from eyeballing and general principles , there seems to be room for intra-Mercurial at 0.188888 AU  (=x^(-1.6666))
                radius of the sun = 0.00464913034 Astronomical Units
It seems that the sun might have shepherd planets close in .
Ideal place for a Solar powerstation or observatory , especially if there are Trojans .

Happy orbits !



Friday, June 14, 2013

Things are worse The Black Death was a bagatelle . Old age kills everybody .

Fast Diet

Gastric Bypass II

Andre Willers
14 Jun 2013
Synopsis :
Diabetes II can be cured by diet that alters gut fauna .
Discussion :
1.Existence Theorem : See appendix A
It has been done .
2. Theory :
See appendix B .
Prolactins play  key role .
Too much lactose and the lactose <-> prolactin balance is disturbed. More than 300 cellular systems are affected . Bad things happen .
An example of an incomplete evolutionary system (ie utilizing lactose , a mammalian food evolved only for babies .)
3. The easiest way is simply to drink maas
The fermentation removes most of the lactose .
Or drink Woolworth’s Lactose free milk .
But then other prolactin-like markers will be missing .

4.Better yet :
The Amasi cocktail : see appendix C
20% Amasi
80% Lactose free milk .
A dash of cinnamon and turmeric.
Alcohol to taste .
Coffee ad hoc .
5. Interesting aside :
The Fasting diet . Eat as you like for 5 days, then fast for two .
Very old . Saturday and Sunday . No work , reduced food .
6.Put the diet on fast forward :
6.1 Everyday , flip a coin “Shall I decide today to fast(Y/N)”
6.2 If N , eat what you like . If Y , flip again “ Shall I fast today ? (Y/N)”
If N , eat . if Y , reduce calories . ie fast .
This means on average per week , 7*1/2*1/2 = 1.75 days of fasting .
But predictably randomly fasting .  
The body treats this as normal hunter-gatherer chance . It makes the body leaner , to be more successful in the hunt . 
This randomizes the fasting . Normally this would mean the body gathering reserves (ie getting fatter) .
But , the body-mind knows this is not a long-term drought . It needs more nimbleness , and less fat .
The whole leveraging thingie goes into reverse leveraging .
Drinking amasi or lactose free milk will accelerate the effect .
7.Pulsations :
Pulsing an anti-acid (kidney regenerator) like a teaspoon of sodium bicarbonate , followed by Amazi and a good pro-biotic on a fasting day will accelerate things .

The effect is cumulative as only beneficial gut-bacteria survive .
The memory of the gut .
Thinly yours



Appendix C

This proudly South African fermented milk product has a smooth, creamy, slightly sour taste. A much-loved tradition in most South African cultures, First Choice Amasi is made by adding a freeze dry culture to the milk and then fermenting it until it reaches a specific acidity level. Our Amasi comes in 1 litre and 2 litre jugs.
Glycaemic Carbohydrate of which:
Total sugar:
Total fat: 


Appendix A

Gut bacteria swap is key to knifeless gastric bypass
·         18:00 27 March 2013 by Douglas Heaven NewScientist .
·         For similar stories, visit the Micro-organisms and Food and Drink Topic Guides
A bacterial cocktail could soon offer a knifeless alternative to gastric bypass surgery.
The gastric bypass limits a person's food intake by, in effect, reducing the size of the stomach – often to the size of a walnut. The procedure is an effective treatment for obesity and associated diseases such as type 2 diabetes, and typically leads to a loss in excess body weight of between 65 and 75 per cent. However, it carries a high mortality risk, especially in severely obese individuals.
Lee Kaplan at Massachusetts General Hospital in Boston and colleagues may have discovered an alternative to surgery. The team performed a gastric bypass on mice and then fed microbes from their lower intestine to other healthy mice. The mice fed the bacterial cocktail lost five per cent of their body weight in two weeks, compared with mice on the same diet who had not been fed the bacteria.
This work is a big step towards a "knifeless bypass", says Carel le Roux at University College Dublin, Ireland, who was not involved in the study. He says that although the gastric bypass cuts calorie intake, it also leads to subtle physiological effects, such as changes in gut bacteria, hormones, bile acids and nerve connections. "It changes how the gut talks to the brain," says le Roux.
It is not yet clear exactly why giving mice gut bacteria from mice that have had a bypass leads to weight loss. The researchers suggest that the gut bacteria present following surgery may reduce the ability of the intestines to absorb calories, or may alter signals regulating metabolism. The goal is to understand what these microbes are doing and duplicate the effects by other means, le Roux says.
Swapping gut bacteria isn't unprecedented as a treatment. In 2010, an 89-year-old woman with a potentially fatal infection received what is known as afaecal transplant from her son. With 24 hours, her fever had abated and the infection soon disappeared. Similar transplants have been successful inminimising symptoms of Parkinson's, multiple sclerosis, chronic fatigue syndrome and rheumatoid arthritis.
Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.3005687
Appendix B
A Cure for Diabetes
Andre Willers
31 May 2012
Synopsis :
The control-system short-circuit that causes diabetes can be interrupted in humans by a simple surgical procedure . This cures diabetes , insulin resistance and high blood pressure . We try to trace why .
Discussion :
1.Read Appendix I . This is a succinct summation of the state–of-play as at May 2012 .
2.Why should bypassing the duodenum have such drastic effects ?
Because the system outsmarted itself . Too many vital feedback loops are being controlled by the same chemicals . (A similar effect is observed in brain-stress and body-stress systems) . Inappropriate responses are triggered . The system is unstable .
2.1Peristaltic action in the duodenum is accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release . See Appendix III . (Note the effect on blood pressure )
But this and PHI release (see Appendix II) affect the Prolactin system ,(see ) which is tied to at least 300 other biochemical processes , as well as the prion system (see “Prions and the Amygdala” May 2012) .
This whole mess is an unstable system , that can and does go wrong in a large number of ways . And the original trigger can be impossible to trace .
2.2To add insult to injury , the original trigger can cause an amygdala reaction : ie a memory remains in the system , and there few , if any , “OFF” switches . Hence nasties like insulin resistance . There are doubtlessly many more . Amygdala’s are notoriously stupid . It is the function of other systems to reprogram them .
See Appendix IV for the ratchet-effect on bloodpressure .
2.3Milk and milk-products can be identified as one of the factors that should cause the system to destabilise .Lactogen breakdown products interfere with some of the feedback loops in the energy metabolism . The result will be idiosyncratic according to individual metabolism , but insulin resistance will ratchet up . (A calf-protection system short-circuits)

What to do ?
Surgery seems a bit drastic . All we want to do is inhibit peristalsis in the duodenum . Food can be massaged through to the jejenum . I can’t find a drug that does this selectively , but I am sure there are some .
But in the meantime we are stuck with something like Loperamide (Imodium) . It is like stopping an enormous factory to fix some small problem at the front-end of the production lines .
The following is not medical advice , and you proceed at your own peril .
Use the pulse principle .
1.Fast until the duodenum is empty , (+-6 hours) . No water .
2.Take Loperimide (Imodium) .. This stops peristalsis and release of neuro-markers .
3.Exercise (walking , jogging – this moves food without peristalsis ) . I have no idea what effect this will have on digestion . But no lying in bed allowed .
4.Then eat and drink mildly on low-carb foods . Appetite will be sharply decreased as alternate demand pathways kick in (Cf Atkins , etc) . Drink when thirsty (cf Noakes) . No milk products of any kind .Verboten
5. How often ? I noticed when writing this that this regimen is remarkably similar to religious regimens like Ramadan , Jewish , Christian , Hindu and Buddhist fasts . Two weeks to a month per year seems adequate . This should reprogram some of the systems to at least a modicum of initial states .
6.Monitor blood glucose about 2 hours after eating .
Interesting Asides :
1.Excessive alcohol intake paralyses the pylorus valve between the stomach and the duodenum . The same effect as fasting , in that food does not enter the duodenum to trigger peristalsis . Typically bloated feeling , with big “beer bellies” . Since alcohol is a product of carbohydrates , this is a fascinating adaptation to high carbohydrate intake .
To put it another way , agricultural farming only took off because periodic alcoholic binges enabled re-normalization of glycemic systems . As this dwindled , so diabetes increased .
2.Milk and Cheese : as use of these increased , systems increasingly crashed in the Prolactin areas . Energy metabolisms became unstable , and auto-immune diseases increased .And you can’t reinstate the original system simply by stopping milk products : amygdala’s have to be reprogrammed .
These are but the a sketch of the bare bones of complex mechanism . But at least some indication of where to go or where not to go .
But I refuse to countenance a system that does not allow toasted cheese sandwiches .
There must be a better way .
Andre .
Appendix I
Cristina Iaboni had the dubious distinction of being not quite obese enough. For all the pounds on her 5'5" frame, she did not meet the criteria for bariatric surgery to help control her type 2 diabetes.
Yet six years of medications and attempts at healthy living had failed to rein in her blood glucose, leaving Iaboni terrified that she was on course to have her kidneys fail "and my feet cut off" -- common consequences of uncontrolled diabetes.
Then the 45-year-old Connecticut wife, mother of two and head of human resources for a Fortune 500 company, lucked out. In 2009 she met with Dr Francisco Rubino of Weill Cornell Medical Center in New York. He had just received approval to study experimental surgery on diabetics with a relatively lean weight-to-height ratio, or body-mass index (BMI). Iaboni was among his first subjects.
Three years on, she has dropped 50 pounds to reach a healthy 145 and has normal blood pressure without medication. That isn't too surprising: Weight loss is the purpose of bariatric surgery and often reduces blood pressure. More remarkable, Iaboni no longer has diabetes.
She is not the first patient with diabetes, which can be triggered by obesity, to be cured by weight-loss surgery. But she is a rarity for having it with a BMI well below 35 and over. That's the level at which the American Diabetes Association says surgery "may be considered" and that Medicare and some private insurers cover. And Iaboni's diabetes disappeared months before she shed much weight.
Her experience has raised an intriguing possibility: that some forms of bariatric surgery treat diabetes not by making patients shed pounds. Instead, by rerouting part of the digestive system, they change what signals the gut sends to the brain and the brain sends to the liver, altering the underlying causes of diabetes.
If proven, bariatric surgery may help people with type 2 diabetes who are less obese, overweight or even of healthy weight. And it might be effective against the currently incurable type 1, or "juvenile," diabetes, too.
"Every textbook says that diabetes is chronic, irreversible, and progressive," said Rubino. "But we have thousands of patients who once had diabetes and now do not."
Bariatric surgeons have long been prone to declaring victory against diabetes way too soon, before large-scale, long-term data proved their case. "The evidence for the success of bariatric surgery in patients with a BMI below 35 is not very strong," said Leonid Poretsky, director of the Friedman Diabetes Institute at Beth Israel Medical Center in New York City. "Most of the studies have been very small and not well controlled."
The American Diabetes Association rates the evidence that bariatric surgery can cure diabetes as "E," the lowest of four grades. It calls data on patients with a BMI below 35 "insufficient," and says the procedure cannot be recommended except as part of research.
The immediate risks of bariatric surgery are small -- a 0.3 per cent chance of dying within 30 days of the procedure. But a small fraction of patients develop infections, leaking from the stomach into the abdominal cavity, or gallstones, and it can cause nutritional deficiencies: There is less intestine to absorb vitamins and minerals, raising the possibility of osteoporosis and anemia.
Despite these red flags, the surgical option is attracting intense interest because the quest to cure diabetes has become almost desperate. In type-1 diabetes, the pancreas does not produce enough insulin, a hormone that moves the glucose in food into cells. In type 2 diabetes, cells become resistant to insulin. In either case, glucose remains in the blood, damaging cells and blood vessels, sometimes severely enough to cause blindness, kidney failure, or gangrene requiring foot or limb amputations.
In 2010, 8.3 per cent of adults worldwide had type 2 diabetes (11.3 per cent did in the United States), resulting in direct medical costs of $376 billion ($116 billion in the United States). By 2030, the global incidence is projected to rise to 9.9 per cent, partly because of the rising obesity rate, with costs reaching $490 billion.
The possibility that bariatric surgery could cure diabetes emerged about a decade ago. A long-term study of thousands of patients in Sweden reported in 2004 that both gastric bypass and banding improved diabetes in many subjects. A 2008 study of 55 obese patients found that 73 per cent of those who underwent gastric banding saw their diabetes disappear after two years, compared to 13 per cent undergoing standard medical treatment such as medication, diet and exercise.
In 2009, surgeons at the University of Minnesota analyzed 621 mostly small studies of bariatric surgery in obese, diabetic patients. Their conclusion, reported in the American Journal of Medicine: 78 per cent no longer needed medication to control their blood sugar. They'd been cured. Lap banding had the worst results, worsening diabetes in some patients.
But most patients in these studies were obese, many morbidly so. (The average BMI was 48.) The improvement in glucose control could therefore be credited to the patients' weight loss, which averaged 85 pounds.
Rubino had a hunch that something else was at work. As a research fellow in diabetes at Mount Sinai Hospital in New York in 1999, he was reviewing the medical literature one day for guidance on how to best perform bariatric surgery on a man with a BMI of 80. He found papers from the 1950s and earlier reporting that surgery for peptic ulcers had cured diabetes.
Ulcer surgery removes a portion of the stomach and reconstructs a connection to the intestine, much as gastric bypass does. Few diabetes experts had noticed the old papers; they were published in surgery journals, which endocrinologists seldom read.
His serendipitous find led Rubino to other papers describing operations on the digestive tract that cured diabetes, something that, according to medical textbooks, was unthinkable.
"Within two weeks of surgery and sometimes sooner, these patients were off their insulin, off their diabetes drugs, and with normal blood glucose levels," said Rubino. "That was too fast to explain by weight loss."
Yet that's how experts explained bariatric surgery's effect on diabetes, especially as the procedure took hold in the 1990s. Few surgeons focused on how quickly the condition disappeared, said Rubino, "or they speculated that patients weren't eating much after the surgery, and that's what cured their diabetes."
He began pursuing the idea that surgery might improve diabetes directly, rather than through weight loss. "I was ignorant of diabetes, so I wasn't burdened by too much knowledge," Rubino said. "Something that might have seemed heretical didn't seem impossible to me."
Rubino modified the popular gastric bypass surgery, called Roux-en-Y, to test his idea on diabetic lab rodents. In the classic operation, the stomach is pinched off so it can hold less food. Surgical cuts keep the rest of the stomach and the top of the small intestine, called the duodenum, from receiving any food. Instead, the stomach empties directly into the bottom of the small intestine, the jejunum. In Rubino's variation, called duodenal-jejunal bypass (DJB), the stomach is untouched, but the rest of the procedure is the same.
The rats that Rubino operated on beginning in 2000 were cured of diabetes much more quickly than their weight fell. It was the first rigorous evidence, from a well-controlled study, that gut surgery has an anti-diabetes effect.
In 2006, Rubino was ready to move from rats to people. Two patients, with BMIs of 29 and 30, underwent his procedure. Their blood sugar levels returned to normal within days, though they lost no weight. In his most recent trial, reported in March in the New England Journal of Medicine, Rubino and colleagues at Catholic University in Rome performed standard gastric bypass surgery or a procedure similar to DJB on people with type 2 diabetes. After two years, 15 of 20 bypass patients and 19 of 20 DJB patients no longer had diabetes.
Curiously, although patients shed pounds, there was no correlation between weight loss and blood glucose, the key marker of diabetes. "Bariatric surgery is more effective on diabetes than obesity," said Rubino. "Patients don't become lean, but they do not have diabetes anymore."
Research from the University of Toronto, reported online this month in Nature Medicine, may finally explain why. It examined the effects of bypass surgery on rats with type-1 diabetes, which is considered even harder to treat than type 2. Normally the jejunum receives only digested mush, as nutrients have already been absorbed in the duodenum, explained lead researcher Tony Lam.
Bypassing the duodenum allows the jejunum to receive an influx of nutrients for the first time, said Lam. Sensing them, the jejunum sends a "got glucose!" signal to the brain. The brain interprets that as a sign of glucose overabundance and orders the liver to decrease glucose production. Result: The rats no longer have diabetes.
"I believe that similar mechanisms are taking place in surgery for type 2 diabetes," said Lam. "It strengthens the case for the surgery treating diabetes independent of weight loss."
His rat study shows why lap banding and stomach stapling are less effective against diabetes than gastric bypass. Banding causes diabetes to go into remission in about 50 per cent of patients, probably due to weight loss, said endocrinologist Dr Allison Goldfine of the Joslin Diabetes Center in Boston.
In contrast, the diabetes-remission rate after Roux-en-Y is 80 to 85 per cent. "The improvements in blood glucose with Roux-en-Y appear to occur very early, by day three after surgery, so patients are being discharged with no medication," she said. Something other than weight loss "must be going on."
Goldfine has launched a study of diabetics with BMIs of 30 to 42 to compare outcomes after lap band surgery, Roux-en-Y, and intense medical management.
A year ago, Rubino began the first large study for type 2 diabetes patients with a BMI as low as 26, where "overweight" begins. The cost of the bypass surgery is covered by a grant from Covidien Plc, which makes laparoscopic instruments and surgical staplers. He aims to enroll at least 50 patients, following them for five years; he has operated on 20 so far.
© Copyright (c) Reuters

Appendix II
Peptide PHI (or peptide histidine isoleucine) is a peptide which functions as a hormone.
It plays a role in the regulation of prolactin in humans.[1]

1.  peptide phi
A 27-amino 
acid peptide with histidine at the N-terminal and isoleucine amide at the C-terminal. The exactamino acid composition of the peptide is species dependent. The peptide is secreted in the intestine, but is foundin the nervous system, many organs, and in the majority of peripheral tissues. It has a wide range of biological actions, affecting the cardiovascular, gastrointestinal, respiratory, and central nervous systems.
Appendix III
Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse
  1. John R. Grider
+Author Affiliations
  1. Departments of Physiology and Medicine, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
  1. Address correspondence to:
    Dr. J. R. Grider, Department of Physiology, P.O. Box 980551, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298. E-mail:
The motor, modulatory, and sensory neurotransmitters that mediate the peristaltic reflex in the mouse colon were identified by direct measurement, and their involvement in various pathways was determined by selective receptor antagonists. Mucosal stimulation in the central compartment of a three-compartment flat sheet preparation of mouse colon elicited ascending contraction and descending relaxation in the orad and caudad compartments, respectively. Ascending contraction was accompanied by substance P release, a marker for excitatory neurotransmitter release, into the orad compartment and was partly inhibited by atropine and spantide, and abolished by a combination of the two antagonists.
Descending relaxation was accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release, into the caudad compartment,
and was partly inhibited by VIP10-28 and NG-nitro-L-arginine, and abolished by a combination of the two agents. Somatostatin release increased during descending relaxation: immunoneutralization of somatostatin or blockade of its effect with a selective somatostatin type 2 receptor antagonist inhibited descending relaxation. The δ-opioid receptor antagonist naltrindole augmented descending relaxation and ascending contraction. Calcitonin gene-related peptide (CGRP) release increased in the central compartment and was mediated by concurrent release of 5-hydroxytryptamine (5-HT) because its release was blocked by a 5-HT4 receptor antagonist. Both the latter and the CGRP antagonist CGRP8-37, inhibited ascending contraction and descending relaxation. Thus, the reflex in mouse like that in rat and human intestine is initiated by mucosal release of 5-HT and activation of 5-HT4 receptors on CGRP sensory neurons and is relayed via somatostatin and opioid interneurons to VIP/nitric-oxide synthase inhibitory motor neurons and via cholinergic interneurons to acetylcholine/tachykinin excitatory motor neurons.


Appendix IV

Peptides. 1984 May-Jun;5(3):593-606.
Co-existence of peptide HI (PHI) and VIP in nerves regulating blood flow and bronchial smooth muscle tone in various mammals including man.
By immunohistochemistry it was found that PHI- and VIP-like immunoreactivity (-IR) occurred in the same autonomic neurons in the upper respiratory tract, tongue and salivary glands with associated ganglia in rat, guinea-pig, cat, pig and man. VIP- and PHI-like immunoreactivity was also found in similar locations in the human heart. The N-terminally directed, but not the C-terminally directed, PHI antiserum or the VIP antiserum stained endocrine cells in the pig duodenum. This suggests the existence of an additional PHI-like peptide. Ligation of nerves acutely caused marked overlapping axonal accumulations of PHI- and VIP-IR central to the lesion. Two weeks after transection of the nerves, both types of immunoreactivities were still observed in accumulations both in the axons as well as in the corresponding cell bodies. The levels of PHI- and VIP-IR in normal tissues from the cat were around 10-50 pmol/g with a molar ratio of about 1 to 2. Systemic administrations of PHI and VIP induced hypotension, probably due to peripheral vasodilation in both guinea-pig and cat. Furthermore, both PHI and VIP caused an inhibition of the vagally induced increase in respiratory insufflation pressure in guinea-pig. PHI and VIP relaxed the guinea-pig trachea in vitro, suggesting a direct action on tracheobronchial smooth muscle. VIP was about 5-10 times more potent than PHI with regard to hypotensive effects and 2-3-fold, considering respiratory smooth muscle-relaxant effects in the guinea-pig. PHI was about 50-fold less potent to induce hypotension in the cat than in the guinea-pig. Although species differences seem to exist as regards biological potency, PHI should also be considered when examining the role of VIP as an autonomic neurotransmitter.