söndag 22 mars 2009

Genkoden

biology200.gsu.edu/.../4564%20'04/lecture12.html Största delen av genomet består av annat än gener.

Det är ett allmänt känt mysterium att vi har för litet gener. Vartefter genkartan blivit känd har antalet blivit mindre och mindre, från c. 100000 till i dag litet över 20000.

Det som skiljer en mänska från en schimpans är också otroligt litet, bara några baspar, 0,6 %. Tidigare trodde man att skillnaden, c. 1,5% av generna, skulle kunna förklara skillnaden, ex. med sk. "nyckelgener". Vartefter schimpansens DNA kartlagts har man kommit underfund med att så inte är fallet. Utvecklingen från schimpans till mänska har krävt också annat än genmutationer.

Gener är starkt överreklamerade. Mänskans DNA är kartlagt, har man trumpeterat ut. Man funderar tom. på att patentera gener. Allt detta är vilseledande tomt prat, kanhända för att få forskningspengar. I dagens läge är gener rätt säkra forskningsobjekt, just genom lättheten att få finansiering.

DNA består mest av - nonsens. Bara 1,2% av DNA:t är gener, extroner. Resten är "skräp", vilket är en felaktig term, för skräpet, intronerna, är den del av genomet som är den viktiga biten. Hela 98,8 % av DNA:t är okänt. Det kodar annat än gener, ex. olika RNA. Också gener kodar RNA för den delen, sk. messengerRNA. Men RNAs produkt är så mycket mera än proteiner. Small RNA är ett ex. De ger en sorts primitivt immunsystem, som man tror fanns innan det immunsystem vi har i dag fanns. Den här sk. interferensen upptäckte man av en slump när man ville få fram extra mörkblåa petunior. De blev till allas förvåning vita, och så fick man upp spåret till detta stora mysterium. En google-sökning i dag på siRNA ger miljoner träffar. Det är en forskning i stark expansion.

Fenotypen är inte alltid beroende av genomet. Kallas non-Mendelisk nedärvning. I det här fallet påverkas slutresultatet (fenotypen) av ett intensivt informationsutbyte mellan kromosom och plastid, ex klorofyll, mitokondrie.
www.biologie.uni-hamburg.de/b-online/e10/10e.htm

Evolutionen tar inte bort någon viktig funktion i första taget, utan funktionerna läggs till. Det kan inte heller vara på något annat sätt, för om en funktion tas bort innan en ny funktion prövats fram genom försök och misstag, kanske den nya funktionen inte visar sig vara livsduglig, och då slutar det illa. Det är inte bara RNA som adderas, utan det gäller alla funktioner. Nervsystem (DC-elektriskt system, nanotuber, meridianer), hormoner (autokrina hormon), signalämnen (eikosanoider) mm. har alla ett modernt system och ett eller flera primitiva system (de inom parentes) som fungerar sida vid sida. Ofta har det nyutvecklade systemet fungerat nästan parallellt med det gamla som därigenom undgått upptäckt, vilket är fallet med nervsystemet. Jämsides med vårt digitala nervsystem (on-off-system) finns det ett analogt likströmssystem. Och dessutom har vi ett "våt-elsystem" i de sk. meridianerna, som kan öppnas eller stängas i sin helhet via piezoelektriska signaler. Gap junctions m.fl. desmosomer är en led i detta system. Här syns igen den fraktala egenskapen i mänskokroppen? Man kan kanske jämföra med en mobiltelefon där över 10 tunna kretskort läggs ovanpå varann. Detta syns inte i funktionen alls.

Skillnaden mellan schimpans och mänska belyser detta på ett bra sätt. Skillnaden finns i intronerna, eller i hur generna används. Mänskans DNA är mera flexibelt än schimpansens DNA. Eller eg. mänskan har ett mera anpassningsbart sätt att använda generna. Intronerna bestämmer hur generna används. Samma gen kan ingå i flera olika protein, och därför kan genprodukten mångdubblas i det sk. proteonomet. Och ännu mera i metabonomet.

Genkoden är inte alls enkel. Finns det flera olika genkoder? Den nuvarande genkoden med tripletter ger 64 möjligheter, men bara 20 aminosyror + start. 3 st möjligheter saknas? I dag finns misstanken om att alla aminosyror inte är likvärdiga, trots att de räknas till samma aminosyra. Den sista koden skiljer? En annan typ av kod kan vara ex. purin-pyrimidin (energikällor). Metylerade (platsen viktig) puriner bryts ner, hos pyrimidiner bryts ringen upp, reduceras av NADPH. Eller topoisomeras-enzymet som får DNA-topologin att ändras? Tyrosin katalyserar omformningen, "klippningen" och avkodningen? Stressen ökar på DNA, konfigurationen ändrar. Nukleosomer med histoner är naturens svar. De låser DNA:t. Allt detta är mycket intressant och har fått ett eget namn; epigenetik. Eller hur generna aktiveras eller inaktiveras. Det är inte generna som är de intressanta delarna, utan det som styr genernas uttryck.

Ser man på intronernas sekvenser blir man inte klok. En upprepning ofta av samma kodord. De liknar mycket telomerernas koder, och telomererna vet vi är ytterst viktiga för kromosomens avkodning vid replikationen. Avkodningen vid syntes av genprodukt styrs enligt samma typ av mekanism, en elektromagnetisk våg? Telepatiska gener? Identiska basmönster förenar?

Intronerna, i dag kallat tilke-DNA, utfyllnads-DNA, kan härstamma från virus. Man har funderat om virus på detta sätt kan gömma sig, för att en dag igen vakna till liv. Gamla, utdöda farsoter kanske en dag oväntat blossar upp på nytt? En stor del av intronerna misstänker man består just av sådant som förändrats så att det inte mera fungerar, ex doftsinnet. Hos däggdjuren fungerar c. 1000 gener, hos schimpanser fungerar bara 65 % mera, hos mänska 40%. Resten är icke funktionsdugliga minnen ur det förflutna? Men kan dessa minnen ibland aktiveras? Växterna kanske har svaret. Samma gener styr utvecklingen av hjärtblad och blomma. För att inte tala om insekternas metamorfos. Fraktala funktioner igen?

Sjukdomar som mänskan, och dess förfäder haft, kan berätta mycket om intronerna och genregleringen. En utdöd sjukdom kanske bekämpades med en viss molekyl. Schimpanserna har ex. en gen som bildar sialinsyra, en antiviral komponent. Mänskan saknar denna gen. Mänskan får mera virussjukdomar, ex. AIDS? Sjukdom befrämjar mutationer, vilket man sett gälla också hos bakterier. De har satt detta i system, så att då någon fara hotar startar en formidabel "mutationsexplosion". Alltid är det någon av de nya varianterna som fungerar.

Schizofreni är en sjukdom som allmänt anses vara en orsak till att arten mänskan föddes. Genier och de schizofrena har något gemensamt.

Också matvanorna syns i intronerna. Maten kan ha gjort så att hjärnan började växa någon gång för 70000 milj.år sedan. Omega 3 havsoljor är en sådan faktor. Därför är omega 3 så hälsosam i dag, och vi äter för litet havsmat, eftersom våra kostrekommendationer är felaktiga. De rekommenderar på tok för mycket kolhydrater. Inte underligt alls att en av faktorerna bakom schizofreni misstänks vara brist på omega 3? Omega 3 från växtriket är inte alls samma sak. De är för långa kedjor. De måste bearbetas extra, och det kräver energi. Nyttan blir då inte samma sak. Och dessutom har oljor från ex.lin och ryps sina egna negativa biverkningar, ex. i fråga om sköldkörtelfunktionen.

Alla däggdjur har FOXP2-genen men det är bara mänskan som kan tala. Samma gen har flera olika funktioner. Hos mänskan har den muterat så att basparen ligger annorlunda. Men skillnaden mänska - schimpans är bara två mutationer som skett för kanske 200000 år sedan. De har gett mänskan egenskaper som hjälpt fram talet?

Mikrocephalia- genen bestämmer hjärnans storlek. Fel på den ger liten hjärna och dvärgväxt. En annan gen bidrar också, MYH-16, vilken producerar proteiner som reglerar käkmuskulaturen. Hos mänskan fungerar inte dessa gener. Köttätandet har bidragit, då de inte längre behövdes, och så muterades de och mutationen korrigerades inte. Hjärnan fick mera rum att växa. Den andliga tillväxten kunde börja. Men generna i sig kan inte ensamma förklara detta.

En stor hjärna kräver mycket energi. Dessa gener måste då omformas. Under utvecklingens gång har de gener som styr hjärnaktiviteten fyrdubblat sin aktivitet. DNA är inte så viktigt? Det viktiga är hur det används? Cis-reglerelement styr? Mänskan har stor varians i sina cis-element. Mänskans genom är mera kreativt och har större möjlighetspotential? Frontalloben och neocortex uttrycker en fraktal funktion?

De funktionella begränsningarna mot olika proteiner har blivit slappare hos mänskan. Vi kan tillåta oss en större variation än schimpansen? Vi har det bättre ställt. Nukleotidsekvenser borde ställas mot fysiologi och biokemi, enl. Satta.

Mänskans nervsystem innehåller c. 100 miljarder celler av 10000 olika typer, men det finns bara ett par tusen reglerande gener. Hur avgörs ödet för en enskild cell? Processen sker i en regleringskedja genom samverkan av 4-7 olika gener. Det kan liknas vid en kryddhylla, där varje krydda har sin egen smak, och blandningar ger sina egna sensationer. Rönen gäller två typer av nervceller hos bananflugor, men angående funktionen skiljer vi oss inte så mycket från bananflugorna.

En av de stora skillnaderna är mänskans behov av att förstå sig själv och sin omgivning. Tolkningarna, de sk. qualias, fenomenen, är viktiga, och här använder vi spegelneuroner som hjälp. Spegelneuroner får sin utformning under barnaåren. Autister har dåligt fungerande spegelneuroner. Det är en fråga om medvetande. Uppfattningsförmågan eller perceptionen, som för det mesta sker i det undermedvetna? Medvetenheten och medvetandet är två olika saker. Signalintensitet som en storskalig integration, eller timing (impulsfrekvens, amplitudfrekvens?) eller något annat? Kanske magnetism? Funktionella cortikala områden, sk. Zeki-noder? Kandidaterna är många.

Referenser:
Angstadt, Carol, 1997: Purine and pyrimidine metabolism. NetBiochem. http//library.med.utah.edu/NetBiochem/pupyr/

Forbes, Ken, 2005: You Descend from Banana or Bonobo? GENEALOGY-DNA-L Archives 2005-01 > 1106711681

Kornyshev, Alexei, 2008: 'Telepathic' genes recognize similarities in each other. BJS. http://www.imperial.ac.uk

Priemé, Anders2005: Se tärkeä ero. Tieteen kuvalehti 2005(2):36-41.

Rees, Geraint et.al. NEURAL CORRELATES OF CONSCIOUSNESS IN HUMANS. www.nature.com/reviews/neuro Nature review, APRIL 2002, VOL 3: 261- 270.

Satta, Yoko, 2001: Comparison of DNA and protein polymorphisms between humans and chimpanzees. Genes & Genetic Systems Vol. 76 (2001) , No. 3 p.159-168

Thor, Stefan 2007: Genkod för nervceller knäckt? Forskning.se, 22.2.2007. Pressmeddelande från Linköpings universitet. PLoS Biology febr. 2007. Magnus Baumgardt et.al. Specification of neuronal identities by feedforward combinatorial coding.

onsdag 4 mars 2009

Liver

The liver plays a major role in metabolism and has a number of functions in the body including detoxification, glycogen storage and plasma protein synthesis. It also produces bile which is important for digestion. It´s main function may be in accommodation of our organism to our surroundings. Therefore also the feelings are so important to the liver. In traditional chinese medicine the liver is our temper, or our heat.

Medical terms related to the liver often start in hepato- or hepatic from the Greek word hepar. The adult human liver normally weighs between 1.0 - 2.5 kilograms. It is unique and the only human organ capable of natural regeneration of lost tissue. The liver thus has a very big flexibility. But this regeneration is not complete, thus the need for transplantings sometimes. When the liver has lost about 70% of its functional capacity this can be seen in liver lab tests, and its renewal is also then disturbed. When liver cells are sclerified they no longer can renew themself, because sclerosis means scar tissue. Earlier stages can be renewed, but the process may be long. Often some kind of lifequality change is required first.

Living donor liver transplantation is a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20% of an adult's liver (Couinaud segments 2 and 3) is needed to serve as a liver allograft for an infant or small child. More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic lobe which amounts to 60% of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. But there have been at least two donor deaths out of the first several hundred cases.

Surface anatomy
Apart from a patch where it connects to the diaphragm, the liver is covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction against other organs. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments. The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe.

If the liver is flipped over, to look at it from behind (the visceral surface), there are two additional lobes between the right and left. These are the caudate lobe (the more superior), and below this the quadrate lobe.

From behind, the lobes are divided up by the ligamentum venosum and ligamentum teres (anything left of these is the left lobe), the transverse fissure (or porta hepatis) divides the caudate from the quadrate lobe, and the right sagittal fossa, which the inferior vena cava runs over, separates these two lobes from the right lobe.

Functional anatomy
It is crucial to understand the organization of liver based on blood supply and biliary drainage, and its fysical support. In the widely used Couinaud or "French" system, the functional lobes are further divided into a total of eight segments based on secondary and tertiary branching of the blood supply.In the growing fetus, a major source of blood to the liver is the umbilical vein which supplies nutrients to the growing fetus. After birth, the umbilical vein and ductus venosus are completely obliterated two to five days postpartum; the former becomes the ligamentum teres and the latter becomes the ligamentum venosum . In the disease state of cirrhosis and portal hypertension, the umbilical vein can open up again.

Physiology
The liver has about 200 different "tasks", and is therefore a very busy organ. It gives warmth to the body. In traditional chinese medicine it gives us the heat, together with the hormonal metabolism.

* The liver produces and excretes bile required for food digestion. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
* The liver performs several roles in carbohydrate metabolism:
o Gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol)
o Glycogenolysis (the formation of glucose from glycogen)
o Glycogenesis (the formation of glycogen from glucose)
o The breakdown of insulin and other hormones
* The liver also performs several roles in lipid metabolism:
o Cholesterol synthesis
o The production of triglycerides (fats).
* The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, and XI, as well as protein C, protein S and antithrombin.
* The liver neutralizes toxins, most medicinal products, and hemoglobin.
* The liver converts ammonia to urea.
* The liver stores of a multitude of substances, including glucose in the form of glycogen, vitamin B12, iron, and copper.
* In the first trimester fetus, the liver is the main site of red blood cell production. By the 42nd week of gestation, the bone marrow has almost completely taken over that task.

Diseases of the liver
Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.

* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
* Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by alcoholism or other toxins, or hepatitis
* Hemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage
* Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract)
* Wilson's disease, a hereditary disease which causes the body to retain copper
* Primary sclerosing cholangitis, an inflammatory disease of the bile duct, autoimmune in nature.
* Primary biliary cirrhosis, autoimmune disease of small bile ducts
* Budd-Chiari syndrome, obstruction of the hepatic vein.
* Steatosis, fatty liver syndrome.

Most liver diseases cause only mild symptoms initially, while it is vital that these diseases are detected early. Hepatic involvement in some diseases can be of crucial importance.

Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays to test the proper function of the liver. These are enzymes that are most abundant in liver tissue, metabolites or products.

Regular liver panel
*Total Protein (TP). The liver produces most of the plasma proteins in the body. So it makes sense to measure the amount of protein in the blood. Reference range (60-80 g/L).
*Albumin (Alb). Albumin is a protein made specifically by the liver. It is the main constituent of total protein; the remaining fraction is called globulin (including e.g. the immunoglobulins). Albumin levels are decreased in chronic liver disease, such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. Poor nutrition or states of protein catabolism may also lead to hypoalbuminaemia. The half-life of albumin is approximately 20 days. Albumin is not considered to be an especially useful marker of liver synthetic function, coagulation factors (see below) are much more sensitive. The reference range is 30-50 g/L.
*Alanine transaminase (ALT), also called Serum Glutamic Pyruvic Transaminase (SGPT) or Alanine aminotransferrase (ALAT) is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or paracetamol overdose. Elevations are often measured in multiples of the upper limit of normal (ULN). The reference range is 15-45 U/L in most laboratories. When liver cell death increases, ALT levels rise above the normal range. The spillover of this enzyme into blood is routinely measured as a marker of abnormal liver-cell damage. For example, alcoholic or viral hepatitis will increase ALT levels, as will severe congestive heart failure. An elevated ALT in the presence of normal levels of plasma alkaline phosphatase helps distinguish liver disease caused by liver-cell damage from diseases caused by problems in biliary ducts.
*Alkaline phosphatase (ALP), is an enzyme in the cells lining the biliary ducts of the liver. If there is an obstruction in the bile duct, e.g. gallstones, ALP levels in plasma will rise. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled). The reference range is usually 30-120 U/L.
*Total bilirubin (TBIL). Bilirubin is a breakdown product of heme (a part of hemoglobin in red blood cells). The liver is responsible for clearing this, excreting it out through bile into the instestine. Problems with the liver or blockage of the drainage of bile will cause increased levels of bilirubin, as will increased haemolysis of red cells.
Direct bilirubin, or unconjugated bilirubin is often measured in tandem, especially if the total bilirubin level is elevated. Bilirubin is unconjugated before the liver modifies it for excretion. It is dangerous in babies, as it can pass the blood-brain barrier causing kernicterus.

Other tests commonly requested alongside LFTs:
*Aspartate transaminase (AST), also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage. It is also present in red cells and cardiac muscle.
*Gamma glutamyl transpeptidase (GGT). Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, Gamma glutamyl transpeptidase (GGT) may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. GGT is raised in alcohol toxicity (acute and chronic).
*Coagulation tests (e.g. INR). The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. If the INR is increased, it means it is taking longer than usual for blood to clot. The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired: it is not a sensitive measure of liver function.
*Hyaluronic Acid Test. Hyaluronic Acid (HA), also called hyaluronate or hyaluronan, is a mucopolysaccharide widely distributed throughout the body. HA is produced mainly by fibroblasts and other specialized connective tissue cells. As a free molecule, HA can be found in the plasma and synovial fluid. HA is quickly removed from circulation by specific receptors present in sinusoidal cells (SEC) of the liver; the estimated half-life in plasma is 5-6 minutes. Increased plasma HA levels may result from one or more of the following:

* Decreased removal of HA from plasma, as a result of liver damage
* Increased production of HA by synovial cells or fibroblasts
Serum HA is elevated in patients with alcoholic liver disease and can be used to detect the progression from alcoholic fatty liver to cirrhosis. Until now, the diagnosis of liver fibrosis and cirrhosis has been established mainly by histologic examination of liver biopsy samples. However, since the fibrotic changes are often distributed unevenly throughout the liver, liver biopsy has been associated with a sampling error of up to 24%. The risk of complications including bleeding and infection, the discomfort to patients and the high cost of hospitalization associated with this invasive procedure limit the use of liver biopsy as a routine screening procedure for cirrhosis. Serum HA levels have been correlated with the degree of fibrosis and cirrhosis in chronic liver disease and may be a non-invasive, less costly method to assess disease status in these patients. Unlike conventional liver function tests, HA levels reflect the function of sinusoidal endothelial cells (SEC) and may be an early marker of toxic liver damage.

Liver failure.
Liver failure can be considered more of a functional syndrome than an anatomical one. Treatment of liver failure includes two components – treating the cause of liver failure and prevention of the development of neurological damage. The second component is more important. Some of the signs of liver failure are:

*General failure of health like weakness, loss of appetite, wasting etc.
*Jaundice
*Bluish discoloration of the nails
*Fever
*Fetor hepaticus – It is a sweetish slightly fecal smell of breath
*Ascites – collection of fluid in the abdominal cavity
*Changes in the protein metabolism
*Skin changes like spider nevi, redness of the palms, white nails etc
*Endocrine changes – In the male, the changes are towards feminization. The changes include small, soft testes, loss of secondary sexual hair, enlargement of breast, diminished sexual desire and potency. In the females, the changes are less and towards gonadal atrophy
*Defective blood clotting

Steatosis.
As the liver becomes more fatty, liver enzymes start to increase and the liver can become inflamed. This inflammation can result in scarring and cirrhosis, or hardening of the liver. Liver function can become compromised. It's estimated that about 10-20 percent of the population of the United States is afflicted with fatty liver syndrome. While fatty liver DOES affect liver function, it's believed that someone who has fatty liver syndrome is not likely to suffer permanent liver damage.
Fatty liver or steatosis hepatis is a reversible condition seen in chronic alcoholism and many other conditions, where large vacuoles of lipid accumulate in hepatocytes (the cells of the liver). The lipid within the vacuoles is a particular type of lipid known as triglyceride. Many chemicals, such as alcohol and drugs can cause fatty liver. Also hormones as thyroxine. TSH is warranted, as hypothyroidism is more prevalent in steatose/NASH patients.
Fatty liver can occur in diabetes mellitus and in pregnancy. It can also be seen in starvation and obesity. In addition, it is also a minor symptom of hepatitis. The treatment of fatty liver depends on what is causing it, and generally, treating the underlying cause will remove the problem.

A fatty liver symptom isn't typically easy to diagnose, because fatty liver disease usually doesn't present many symptoms in the early stages. As a result, many people with fatty liver don't realize they're developing a liver problem. When a fatty liver symptom does appear, it might be

* Abdominal swelling
* Fever
* Jaundice, or yellowing of the skin
* Overall itchiness
* Right-side abdominal pain
* Small yellow skin nodules

Any of these should be considered a possible fatty liver symptom. If any of these symptoms should appear, the patient is advised to have liver function tests done. If fatty liver is present, the test results will show an enlarged liver or minor elevation of liver enzymes.

Non-alcoholic steatohepatitis (NASH)is fatty inflammation of the liver when this is not due to excessive alcohol use. It is a major cause of cryptogenic cirrhosis of the liver. In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications.
It differs from the simple accumulation of fat in the liver (fatty liver, or hepatic steatosis) in that the inflammation of NASH causes damage to the liver cells. Sometimes dull right upper quadrant pain is felt, occasionally radiating to the right shoulder. Mild icterus (jaundice) can sometimes be noticed.

NASH is associated with metabolic syndrome X, diabetes mellitus (type II) and insulin resistance. Disturbed liver enzymes are common. The main cause is insulin resistance, which explains co-occurrence of NASH and syndrome X. NASH was described in 1980 (the Mayo Clinic).

NASH can also be caused by the following medications:

* Amiodarone, a class III antiarrhythmic agent used in the treatment of ventricular arrhythmias and the suppression of atrial and ventricular arrhythmias.
* Antiviral drugs (nucleoside analogues ), Most of the antivirals now available are designed to help deal with HIV; herpesvirus, which are best known for causing cold sores but actually cover a wide range of diseases; and the hepatitis B and C viruses, which can cause liver cancer.
* Aspirin / NSAIDS. Aspirin was the first discovered member of the class of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs), not all of which are salicylates, though they all have similar effects and a similar action mechanism. Aspirin suppresses the production of prostaglandins and thromboxanes. This happens because cyclooxygenase (COX-1), an enzyme which participates in the production of prostaglandins and thromboxanes, is irreversibly inhibited when aspirin acetylates it. Prostaglandins are local hormones (paracrine) produced in the body and have diverse effects in the body, including but not limited to transmission of pain information to the brain, modulation of the hypothalamic thermostat and inflammation. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are primarily caused by blood clots, and their reduction with the introduction of small amounts of aspirin has been seen to be an effective medical intervention. The side effect of this is that the ability of the blood in general to clot is reduced, and excessive bleeding may result from the use of aspirin. More recent work has shown that there are at least two different types of cyclooxygenase: COX-1 and COX-2. Aspirin inhibits both of them.

Newer NSAID drugs called COX-2 selective inhibitors have been developed that only inhibit COX-2, with the hope that this would reduce the gastrointestinal side effects.

However, several of the new COX-2 selective inhibitors have been recently withdrawn, after evidence emerged that COX-2 inhibitors increase the risk of heart attack. It is proposed that endothelial cells lining the arteries in the body express COX-2, and by selectively inhibiting COX-2, prostaglandins (specifically PGF2) are downregulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anti-coagulative effect of PGF2 is decreased, increasing the risk of thrombus and associated heart attacks and other circulatory problems.
* Corticosteroids. are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. They work through the same eikosanoid-circles as above.
* Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.
* Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney.
* Methotrexate, to treat many kinds of cancers.
* Nifedipine, is a dihydropyridine calcium channel blocker. Its main uses are in angina pectoris and hypertension, although a large number of other uses have recently been found for this agent, such as Raynaud's phenomenon, and esophagus-spasms.
* Perhexiline maleate
* Tamoxifen, is an oral selective estrogen receptor modulator which is used in breast cancer.
* Tetracycline is an antibiotic produced by the streptomyces bacterium.
* Valproic acid is a sodium salt of valproic acid. is a anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder; but also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal ), complex partial seizures , and the seizures associated with Lennox-Gastaut syndrome .

Valproate is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain.

Cirrhosis.
Cirrhosis is a chronic disease of the liver in which liver tissue is replaced by connective tissue, resulting in the loss of liver function. Cirrhosis is caused by damage from toxins (including alcohol), metabolic problems, chronic viral hepatitis or other causes. Cirrhosis is sometimes referred to by its obsolete eponym Laennec's cirrhosis after René Laënnec. Cirrhosis is irreversible but treatment of the causative disease will slow or even halt the damage.

Cirrhosis has many possible causes; sometimes more than one cause are present in the same patient. Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates. The hepatitis B virus is probably the most common cause of cirrhosis worldwide, especially South-East Asia. Inherited diseases. These interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.

* Alpha 1-antitrypsin deficiency
* Hemochromatosis (iron accumulation)
* Wilson's disease (copper accumulation)
* Galactosemia
* Glycogen storage diseases
* Cystic fibrosis

Early symptoms include red palms , spider angioma (red spots on the upper body), hypertrophy of the parotid glands, and fibrosis of tendons in the hands. Clubbing may develop.

Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces healthy cells, liver function starts to fail and a person may experience the following symptoms:

* exhaustion
* fatigue
* loss of appetite
* nausea
* weakness
* weight loss
* abdominal pain

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.

* Bruising and bleeding due to decreased production of coagulation factors.
* Jaundice due to decreased processing of bilirubin.
* Itching due to bile products deposited in the skin.
* Hepatic encephalopathy - the liver does not clear ammonia and related nitrogenous substances from the blood, which affect cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
* Sensitivity to medication due to decreased metabolism of the active compounds.
* Insulin resistance and type 2 diabetes.
* Hepatocellular carcinoma is primary liver cancer, commonly caused by cirrhosis. It has a high mortality rate.
* Portal hypertension - blood normally carried from the intestines and spleen through the portal vein flows more slowly and the pressure increases; this leads to the following complications:
o Ascites - fluid leaks through the vasculature into the abdominal cavity.
o Esophageal varices - collateral portal blood flow through vessels in the stomach and esophagus. These blood vessels may become enlarged and are more likely to burst.
* Problems in other organs. Cirrhosis can cause immune system dysfunction, leading to infection. Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines (spontaneous bacterial peritonitis). Cirrhosis can also lead to impotence, kidney dysfunction and renal failure (hepatorenal syndrome ) and osteoporosis.
# Drugs or toxins.
# Repeated bouts of heart failure with liver congestion.
# Certain parasitic infections (like schistosomiasis).

Vitamins and nutrient supplies.
Doctors often claim that excess vitamins and nutrients may be dangerous. And of course it may be so. But I have tried to look for such natural remedy issues without success. I have found simply nothing.

The main reason for such interferens is
* excess fat-soluble vitamins as vit A.
* excess betacaroten as an antioxidant. Observe that antioxidants in a way neutralize the workings of free radicals, that our body itself manufacture, and which is needed by our immune system. Excess of antioxidants means eventually that cancercells avoid destruction.
* webshop remedies are not always safe. In the best they can continue absolutely no essential essence, but at worst they can continue heavily toxins or parasites. Remedies bought from webshops abroad is done at own risk.
* Individual differences, partly heredical. For example differences in detoxification system due to cytocrom differences. Also deseaces may change the tolerance to high doses of vitamins/nutrients. In the same way some sick people or older people may have an increased demand for vitamins/nutrient supply.

Used in the way terapeuts or doctors ordinate vitamins are usually safe to use.

References:
Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434-438. PMID 7382552.

http://www.biologydaily.com/biology/Liver

WikiLiver: A Wiki dedicated to the liver

http://www.healthinfoarticles.com/liver.html

söndag 1 mars 2009

The fractal brain

Is the brain self-similar, or fractal?
The complexity of human brain geometry suggests a description based on fractality, a mathematical construction to describe self-similarity in various objects in dead and living matter. This would mean that properties or patterns of small cortex structures would be equal to larger ones. Topology is another character. That is the possibility to recognize different forms in smaller, as well as in larger areas, thou somewhat tortoised. This picture refers to average picture of function and structure in brain, not detailed anatomy or fysiology.


Fractal brain, fractal art. It looks like the brain is made of energy, and that energy is shooting outwards from the brain.

During 1990-decade several authors found fractal geometry of brain highly probable. Surface-to volume ratio, external cortex surface, 3-D analysis of fixed brains, interface between grey and white matter, etc. From these it seems that white matter has indeed a fractal geometry, but perhaps not including all the brain. In neuroscience, researchers have examined the structure of axonal networks connecting individual neurons and whole-brain networks of interregional pathways.
Verification is needed.

The geometry of human cortical grey matter was the subject for Kiselev 2008. Analysis including all spatial scales from size of the brain to the ultimate image resolution showed fractality down to scale size 2,5 mm, corresponding to the cortex thickness. Also the folding of the brain shows fractality for the largest spatial scales. Note that two individuals are never identical, nor has cortex the same thickness everywhere. The foldings can be described as dilations, showing different characteristics for inner and outer surfaces of cortex. Averages may show errors. As a whole fractality exists in both area and volume of the brain.

There is also a possibility for correlations with brain deseases.

Brain function.
Brain function depends on adaptive self-organization of large-scale neural assemblies, but little is known about quantitative network parameters governing these processes in humans. Here, the topology and synchronizability of frequency-specific brain functional networks.
Brain functional networks were characterized by small-world properties at all six wavelet scales considered, corresponding approximately to classical δ (low and high), θ, α, β, and γ frequency bands. Global topological parameters (path length, clustering) were conserved across scales, most consistently in the frequency range 2–37 Hz, implying a scale-invariant or fractal small-world organization. Dynamical analysis showed that networks were located close to the threshold of order/disorder transition in all frequency bands. The highest-frequency γ network had greater synchronizability, greater clustering of connections, and shorter path length than networks in the scaling regime of (lower) frequencies. Behavioral state did not strongly influence global topology or synchronizability; however, motor task performance was associated with emergence of long-range connections in both β and γ networks. Long-range connectivity, e.g., between frontal and parietal cortex, at high frequencies during a motor task may facilitate sensorimotor binding.

Human brain functional networks demonstrate a fractal small-world architecture that supports critical dynamics and task-related spatial reconfiguration while preserving global topological parameters.

The small-world topology of brain functional networks is largely preserved across multiple frequency bands and behavioral tasks. The canonical small-world network is one in which the majority of edges are recruited to form small, densely connected clusters, whereas the remainder are involved in maintaining connections between these clusters.

Patterns of functional connectivity across a large number of recording sites were obtained for each of six distinct temporal scales ranging over all classical EEG frequency bands, from low (1.1–2.2 Hz) to gamma (37.5–75 Hz). These correlations between signals in wavelet space express a statistical association between recording sites, a signature of dynamical interactions between brain regions. The authors then transform the continuous symmetric matrix of wavelet correlations obtained for each frequency band to a binary symmetric matrix by applying a threshold

Small-world attributes reflect the need of the network to satisfy simultaneously the opposing demands of local and global processing and that they may reflect an organization that tends to minimize the number of processing steps. Given the spatial complexity of neural dynamics, it seems likely that functionally relevant communication would have to occur across multiple frequency bands. Correlations to EEG - EMG - EXG ??? If the small-world functional architecture revealed by Bassett et al. indeed promotes efficient interregional communication, then it should be found across multiple temporal scales.

It appears that brain networks preserve global topological characteristics (continually maintaining the balance of efficient local and global processing) while flexibly adapting the specifics of the topology to satisfy changing task demands. Interestingly, it appears that higher-frequency bands (beta and gamma) exhibit more extensive changes in connection patterns across tasks, specifically in the form of new long-range functional relationships between sensory and motor regions during the execution of a motor task.

The idea that perception and cognition depend critically on patterns of synchronization and desynchronization, fits perfectly in this picture. The dynamic coupling and uncoupling of distant neural sites reflect changes in sensory inputs, task demands, thinking or attention. The fact that these synchronization patterns occur at multiple frequencies might mean that brain functional networks contain multiple ‘‘frequency channels’’ along which information is transmitted. What happens when the global topology of human brain functional networks changes across all frequency bands or within a specific range of frequencies. Empirical evidence suggests that such changes in global network topology occur between sleep and waking.

Is form a reason for function?
Can function be revealed by structure? This is an old question, not yet answered. In brain we have Broadmanns areas that certainly suggest functions. A small-world network has been suggested to be an efficient solution for achieving both modular and global processing—a property highly desirable for brain computations.

Functional connectivity has previously been shown to correlate with structural (anatomical) connectivity patterns at an aggregate level.
1. strong functional connections commonly exist between regions with no direct structural connection, rendering the inference of structural connectivity from functional connectivity impractical;
2. indirect connections and interregional distance accounted for some of the variance in functional connectivity that was unexplained by direct structural connectivity;
3. resting-state functional connectivity exhibits variability within and across both scanning sessions and model runs.

These empirical and modeling results demonstrate that although resting state functional connectivity is variable and is frequently present between regions without direct structural linkage, its strength, persistence, and spatial statistics are nevertheless constrained by the large-scale anatomical structure of the human cerebral cortex.

Self-organization is a inherent principle in brain and in whole universe? This question links to the traditional chinese medicine (Yin and Yang) and the entropy model of body/mind/brain.

References:
Bassett DS, Meyer-Lindenberg A, Achard S, Duke
T, Bullmore E. 2006: Adaptive reconfiguration of fractal small-world human brain functional networks. PNAS 2006, vol. 103 no. 51:19518-19523 http://www.pnas.org/content/103/51/19518.abstract
Comment PNAS 2006 vol. 103 no. 51:19219–19220, Olaf Sporns and Christopher J. Honey.
Small worlds inside big brains.

Luke Gardiner by deviantART. http://rustkill.deviantart.com/art/Fractal-Brain-7070062 Fractal brain, fractal art
It looks like the brain is made of energy, and that energy is shooting outwards from the brain.

Honey, C. J., O. Sporns, L. Cammoun, X. Gigandet, J. P. Thiran, R. Meuli, and P. Hagmann (2009): Predicting human resting-state functional connectivity from structural connectivity. Proc. Natl. Acad. Sci. USA 2009 106:2035-2040 http://www.pnas.org/content/106/6/2035.abstract

Kiselev, V. G.; Hahn, Klaus und Auer, Dorothee P. (2002): Is the Brain Cortex a Fractal? Sonderforschungsbereich 386, Discussion Paper 297. 18. November 2008 http://epub.ub.uni-muenchen.de/1675/

Massimini M, Ferrarelli F, Huber R, Esser SK, Singh H, Tononi G (2005) Science 309:2228–2232.