EDTA molecule

EDTA is a widely used abbreviation for the chemical compound ethylenediaminetetraacetic acid (and many other names, see table). EDTA refers to the chelating agent with the formula (HO2CCH2)2NCH2CH2N(CH2CO2H)2. This amino acid is widely used to sequester di- and trivalent metal ions (Ca2+ and Mg2+ for example). EDTA binds to metals via four carboxylate and two amine groups. EDTA forms especially strong complexes with Mn(II), Cu(II), Fe(III), Pb (II) and Co(III).


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Synthesis

EDTA is mostly synthesised from 1,2-diaminoethane (ethylenediamine), formaldehyde (methanal), water and sodium cyanide.[2] This yields the tetra sodium salt, which can be converted into the acidic forms by acidification. Pioneering work on the development of EDTA was undertaken by Gerold Schwarzenbach in the 1940s.

Isomer
EDTA exists in different standard forms under different conditions. At very low pH or very acidic condition (fully protonated) H6Y+2 forms exist while at very high pH or very basic condition (fully deprotonated) Y-4 forms are prevalent.

Nomenclature
To describe EDTA and its various protonated forms, chemists use a more cumbersome but more precise acronym that distinguishes between EDTA4−, the conjugate base that is the ligand, and H4EDTA, the precursor to that ligand.

Lysine Animation

Lysine is a base, as are arginine and histidine. The ε-amino group often participates in hydrogen bonding and as a general base in catalysis. Common posttranslational modifications include methylation of the ε-amino group, giving methyl-, dimethyl-, and trimethyllysine. The latter occurs in calmodulin. Other posttranslational modifications at lysine residues include acetylation and ubiquitination. Collagen contains hydroxylysine which is derived from lysine by lysyl hydroxylase. O-Glycosylation of lysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain proteins for secretion from the cell.


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Lysine an α-amino acid with the chemical formula HO2CCH(NH2)(CH2)4NH2. This amino acid is an essential amino acid, which means that humans cannot synthesize it. Its codons are AAA and AAG.
L-Lysine is a necessary building block for all protein in the body. L-Lysine plays a major role in calcium absorption; building muscle protein; recovering from surgery or sports injuries; and the body's production of hormones, enzymes, and antibodies. Lysine can be modified through acetylation, methylation, ubiquitination, sumoylation, neddylation, biotinylation and carboxylation which tends to modify the function of the protein of which the modified lysine residue(s) are a part.
Clinical significance
It has been suggested that lysine may be beneficial for those with herpes simplex infections.[, more research is needed to fully substantiate this claim. For more information, refer to Herpes simplex - Lysine.
There are Lysine conjugates that show promise in the treatment of cancer, by causing cancerous cells to destroy themselves when the drug is combined with the use of phototherapy, while leaving non-cancerous cells unharmed.

Breast Biopsy Procedure

A biopsy is surgery to remove a sample of tissue. A pathologist examines the biopsied tissue under a microscope to see if any cancer is present.The diagnosis of breast cancer depends upon examination of tissue or cells removed by biopsy. A biopsy is the only way to know for sure if a breast change is benign or malignant.

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Description of Breast Biopsy
There are a number of methods, depending upon the size and location of the lump or suspicious area, and the general health of the patient. These include:

Aspiration: The use of a needle and syringe to try to drain the lump

Fine-needle aspiration: The use of a thin needle and syringe to collect cell clumps or single cells from the lump. Used for cysts and sometimes to sample cells from masses with or without calcifications.

Aspiration is the fastest and easiest method to perform biopsies, with rapid results and no stitches or scarring. However, the small sample size can lead to incomplete assessment or misdiagnosis.

Core needle biopsy: The removal of a small piece of breast tissue using a needle that has a special cutting edge. It takes sample tissue from solid mass or calcium deposits. There are several needle insertions, but no stitches or internal scar. The larger sample can lead to more accurate diagnosis, although it is still limited enough to possibly underestimate more serious diagnosis.
Vacuum assisted biopsy: The removal of multiple samples of breast tissue via a fairly new technique. Excellent for calcium deposits; can remove several large samples with one needle insertion; no stitches and minimal scarring. It may be less accurate than surgical biopsy to remove the entire lesion, and is not ideal for hard-to-reach area (i.e., near chest wall).

Excisional biopsy: The removal of the entire lump. Used most often, it is the current "standard" procedure for small (less than about an inch in diameter) lumps. Also called a lumpectomy.

Incisional biopsy: The removal of part of the lump. This method may be used if the breast lump is large.

Both excisional and incisional biopsies are called open surgical biopsies. They are used for masses, hard-to-reach lesions, multiple lesions and masses with micro-calcifications. They give the largest tissue sample, which gives the near 100% diagnosis. These require stitches and a longer recovery, and permanent scarring may make future mammograms difficult to read.

Mammographic localization with biopsy: Used when a possible breast tissue abnormality can be seen on a mammogram but cannot be felt. The mammogram is used as a guide for placing small needles at the site of the breast abnormality. Sometimes, dye is used instead of needles to mark the site. The suspicious tissue can then be removed surgically for examination. Another mammogram of the specimen is obtained to document that the lesion was excised.

Computerized Stereotactic Modifications have been added to mammographic units in order to localize abnormalities and perform needle biopsy without surgery. Under mammographic guidance, a biopsy needle can be inserted into the lesion in the mammographer's suite, and a core of tissue or cells can be examined.

Genographic Project

div style="text-align: justify;">The Genographic Project, launched in April 2005, is a five-year genetic anthropology study that aims to map historical human migration patterns by collecting and analyzing DNA samples from hundreds of thousands of people from around the world.

Field researchers at 10 regional centers around the world collect DNA samples from indigenous populations. The project also sells self-testing kits: for US$100 anyone in the world can order a kit with which a mouth scraping (buccal swab) is obtained, analyzed and the DNA information placed on an Internet accessible database. The genetic markers on mitochondrial DNA (HVR1) and Y-chromosomes (12 microsatellite markers and haplogroup-defining SNPs) are used to trace the customer's distant ancestry, and each customer is provided with their genetic history. As of August 2008 more than 265,000 people had bought a test kit.
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The US$40M project is a privately-funded, not-for-profit collaboration between the National Geographic Society, IBM and the Waitt Family Foundation. Part of the proceeds from the sale of self-testing kits support the Genographic Project's ongoing DNA collection, but the majority are ploughed into a Legacy Fund to be spent on cultural preservation projects nominated by indigenous communities.

Stem Cells: Regeneration Cancer and Natural Selection

Dr. Irving Weissman, Professor of Pathology and Developmental Biology at Stanford University and Director of the Stanford Comprehensive Cancer Center discusses current research in stem cell biology and the effects of public policy on research.

Leucine

Leucine (abbreviated as Leu or L) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH(CH3)2. It is an essential amino acid, which means that humans cannot synthesise it. Its codons are UUA, UUG, CUU, CUC, CUA, and CUG. With a hydrocarbon side chain, leucine is classified as a hydrophobic amino acid. It has an isobutyl R group. Leucine is a major component of the sub units in ferritin, astacin and other 'buffer' proteins.



  Subscribe in a reader Biosynthesis

As an essential amino acid, leucine is not synthesized in animals, hence it must be ingested, usually as a component of proteins. It is synthesized in plants and microorganisms via several steps starting from pyruvic acid. The initial part of the pathway also leads to valine. The intermediate α-ketovalerate is converted to α-isopropylmalate and then β-isopropylmalate, which is dehydrogenated to α-ketoisocaproate, which in the final step undergoes reductive amination. Enzymes involved in a typical leucine biosynthesis include.
  • Acetolactate synthase,
  • Acetohydroxy acid isomeroreductase,
  • Dihydroxyacid dehydratase,
  • α-Isopropylmalate synthase,
  • α-Isopropylmalate isomerase,
  • Leucine aminotransferase.
As a dietary supplement, leucine has been found to slow the degradation of muscle tissue by increasing the synthesis of muscle proteins. Leucine is utilized in the liver, adipose tissue, and muscle tissue. In adipose and muscle tissue, leucine is used in the formation of sterols, and the combined usage of leucine in these two tissues is seven times greater than its use in the liver.

Hepatitis B and C

Hepatitis B virus infects the liver of hominoidae, including humans, and causes an inflammation called hepatitis. It is a DNA virus and one of many unrelated viruses that cause viral hepatitis. The disease, originally known as "serum hepatitis", has caused epidemics in parts of Asia and Africa, and it is endemic in China. About a third of the world's population, more than 2 billion people, have been infected with the hepatitis B virus. This includes 350 million chronic carriers of the virus. The acute illness causes liver inflammation, vomiting, jaundice and—rarely—death. Chronic hepatitis B may eventually cause liver cirrhosis and liver cancer—a fatal disease with very poor response to current chemotherapy.The infection is preventable by vaccination.


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Hepatitis C is a blood-borne infectious disease that is caused by the hepatitis C virus (HCV), affecting the liver. The infection is often asymptomatic, but once established, chronic infection can cause inflammation of the liver (chronic hepatitis). This condition can progress to scarring of the liver (fibrosis), and advanced scarring (cirrhosis). In some cases, those with cirrhosis will go on to develop liver failure or other complications of cirrhosis, including liver cancer.

The hepatitis C virus (HCV) is spread by blood-to-blood contact. No vaccine against hepatitis C is available. The symptoms of infection can be medically managed, and a proportion of patients can be cleared of the virus by a course of anti-viral medicines. Although early medical intervention is helpful, people with HCV infection can experience mild symptoms, and consequently do not seek treatment. An estimated 150-200 million people worldwide are infected with hepatitis C.

Melamine

Melamine is an organic base and a trimer of cyanamide, with a 1,3,5-triazine skeleton. Like cyanamide, it contains 66% nitrogen by mass and, if mixed with resins, has fire retardant properties due to its release of nitrogen gas when burned or charred, and has several other industrial uses. Melamine is also a metabolite of cyromazine, a pesticide. It is formed in the body of mammals who have ingested cyromazine. It has been reported that cyromazine can also be converted to melamine in plants.

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Melamine combines with cyanuric acid to form melamine cyanurate, which has been implicated in the Chinese protein export contaminations.

Melamine is combined with formaldehyde to produce melamine resin, a very durable thermosetting plastic used in Formica, and melamine foam, a polymeric cleaning product. The end products include countertops, dry erase boards, fabrics, glues, housewares and flame retardants. Melamine is one of the major components in Pigment Yellow 150, a colorant in inks and plastics.

Melamine also enters the fabrication of melamine poly-sulfonate used as superplasticizer for making high-resistance concrete. Sulfonated melamine formaldehyde (SMF) is a polymer used as cement admixture to reduce the water content in concrete while increasing the fluidity and the workability of the mix during its handling and pouring. It results in concrete with a lower porosity and a higher mechanical strength exhibiting an improved resistance to aggressive environments and a longer life-time.

The use of melamine as fertilizer for crops had been envisaged during the '50s and '60s because of its high nitrogen content (2/3).However, the hydrolysis reactions of melamine leading to the nitrogen mineralisation in soils are very slow, precluding a broad use of melamine as fertilizing agent.

Melamine derivatives of arsenical drugs are potentially important in the treatment of African trypanosomiasis.

Melamine use as non-protein nitrogen (NPN) for cattle was described in a 1958 patent. In 1978, however, a study concluded that melamine "may not be an acceptable non-protein N source for ruminants" because its hydrolysis in cattle is slower and less complete than other nitrogen sources such as cottonseed meal and urea.

Melamine is sometimes illegally added to food products in order to increase the apparent protein content. Standard tests such as the Kjeldahl and Dumas tests estimate protein levels by measuring the nitrogen content, so they can be misled by adding nitrogen-rich compounds such as melamine.

Toxicity
Melamine is described as being "Harmful if swallowed, inhaled or absorbed through the skin. Chronic exposure may cause cancer or reproductive damage. Eye, skin and respiratory irritant.” However, the toxic dose is on a par with common table salt with an LD50 of more than 3 grams per kilogram of bodyweight.FDA scientists explained that when melamine and cyanuric acid are absorbed into the bloodstream, they concentrate and interact in the urine-filled renal microtubules, then crystallize and form large numbers of round, yellow crystals, which in turn block and damage the renal cells that line the tubes, causing the kidneys to malfunction.

The European Union set a standard for acceptable human consumption of melamine at 0.5 milligrams per kg of body mass, Canada declared a limit of 0.35 mg and the US FDA’s limit was put at 0.63 mg, but was later reduced to 0.063 mg daily. The World Health Organization’s food safety director estimated that the amount of melamine a person could stand per day without incurring a bigger health risk, the "tolerable daily intake" (TDI), was 0.2 mg per kg of body mass.

Melamine is reported to have an oral LD50 of 3248 mg/kg based on rat data. It is also an irritant when inhaled or in contact with the skin or eyes. The reported dermal LD50 is >1000 mg/kg for rabbits.[15] In a 1945 study. A study by USSR researchers in the 1980s suggested that melamine cyanurate, commonly used as a fire retardant, could be more toxic than either melamine or cyanuric acid alone.[17] For rats and mice, the reported LD50 for melamine cyanurate was 4.1 g/kg (given inside the stomach) and 3.5 g/kg (via inhalation), compared to 6.0 and 4.3 g/kg for melamine and 7.7 and 3.4 g/kg for cyanuric acid, respectively.

A toxicology study conducted after recalls of contaminated pet food concluded that the combination of melamine and cyanuric acid in diet does lead to acute renal failure in cats.

Coronary Stent

Coronary heart disease can result in the blockage of arteries. Insertion of a stent can open up the clogged artery. The blockage can re-form but this re-blockage can be inhibited if the stent is coated with a chemotherapy drug.
Treating a blocked ("stenosed") coronary artery with a stent follows the same steps as other angioplasty procedures with a few important differences. The interventional cardiologist uses angiography to assess the location and estimate the size of the blockage ("lesion") by injecting a contrast medium through the guide catheter and viewing the flow of blood through the downstream coronary arteries. Intravascular ultrasound (IVUS) may be used to assess the lesion's thickness and hardness ("calcification").

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The cardiologist uses this information to decide whether to treat the lesion with a stent, and if so, what kind and size. Drug eluting stents are most often sold as a unit, with the stent in its collapsed form attached onto the outside of a balloon catheter. Outside the US, physicians may perform "direct stenting" where the stent is threaded through the lesion and expanded. Common practice in the US is to predilate the blockage before delivering the stent. Predilation is accomplished by threading the lesion with an ordinary balloon catheter and expanding it to the vessel's original diameter. The physician withdraws this catheter and threads the stent on its balloon catheter through the lesion. The physician expands the balloon which deforms the metal stent to its expanded size. The cardiologist may "customize" the fit of the stent to match the blood vessel's shape, using IVUS to guide the work.It is critically important that the framework of the stent be in direct contact with the walls of the vessel to minimize potential complications such as blood clot formation. Very long lesions may require more than one stent -- this result of this treatment is sometimes referred to as a "full metal jacket".

The procedure itself is performed in a catheterization clinic ("cath lab"). Barring complications, patients undergoing catheterizations are kept at least overnight for observation.

Dealing with lesions near branches in the coronary arteries presents additional challenges and requires additional techniques

Stem Cells Brain's Beginnings

"Stem cells:the brains beginnings" is presented by Fred Gage,Ph.D,from salk institute for biological studies.Fred H. Gage is a professor in the Laboratory of Genetics at the Salk Institute, and has concentrated on the adult central nervous system and the unexpected plasticity and adaptability that remains throughout the life of all mammals. His work may lead to methods of replacing brain tissue lost to stroke or Alzheimer’s disease and repairing spinal cords damaged by trauma.



In this lecture he talk about"what role do stem cells play in development of the brain?."


Research
In 1998, Fred H. Gage (Salk Institute for Biological Studies, La Jolla, California) and Peter Eriksson (Sahlgrenska University Hospital, Gothenburg, Sweden) discovered and announced that the human brain produces new nerve cells in adulthood. Until then, it had been assumed that humans are born with all the brain cells they will ever have.

Gage’s lab showed that, contrary to years of dogma, human beings are capable of growing new nerve cells throughout life. Small populations of immature nerve cells are found in the adult mammalian brain, and Gage is working to understand how these cells can be induced to become mature nerve cells. His team is investigating how such cells can be transplanted back to the brain and spinal cord. They have showed that physical exercise can enhance the growth of new brain cells in the hippocampus, a brain structure that is important for the formation of new memories. Furthermore, his team is examining the underlying molecular mechanisms that are critical to the birth of new brain cells, work that may lead to new therapeutics for neurodegenerative conditions.


"Fred Gage." Wikipedia, The Free Encyclopedia. 6 Jan 2009, 06:04 UTC. 8 Jan 2009 http://en.wikipedia.org/w/index.php?title=Fred_Gage&oldid=262252770.

Embryonic Stem Cells for Treating Diabetes

Dr. Michael German, the clinical director of UC San Francisco's Diabetes Center, as he explores the steps human embryonic stem cells take to become insulin producing pancreatic islet cells, and the goal of clinicians to transplant these cells to treat diabetes
The discovery of methods to isolate and grow human embryonic stem cells in 1998 renewed the hopes of doctors, researchers, and diabetes patients and their families that a cure for type 1 diabetes, and perhaps type 2 diabetes as well, may be within striking distance. In theory, embryonic stem cells could be cultivated and coaxed into developing into the insulin-producing islet cells of the pancreas. With a ready supply of cultured stem cells at hand, the theory is that a line of embryonic stem cells could be grown up as needed for anyone requiring a transplant. The cells could be engineered to avoid immune rejection. Before transplantation, they could be placed into nonimmunogenic material so that they would not be rejected and the patient would avoid the devastating effects of immunosuppressant drugs. There is also some evidence that differentiated cells derived from embryonic stem cells might be less likely to cause immune rejection (see Chapter 10. Assessing Human Stem Cell Safety). Although having a replenishable supply of insulin-producing cells for transplant into humans may be a long way off, researchers have been making remarkable progress in their quest for it. While some researchers have pursued the research on embryonic stem cells, other researchers have focused on insulin-producing precursor cells that occur naturally in adult and fetal tissues.
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Since their discovery three years ago, several teams of researchers have been investigating the possibility that human embryonic stem cells could be developed as a therapy for treating diabetes. Recent studies in mice show that embryonic stem cells can be coaxed into differentiating into insulin-producing beta cells, and new reports indicate that this strategy may be possible using human embryonic cells as well.

Last year, researchers in Spain reported using mouse embryonic stem cells that were engineered to allow researchers to select for cells that were differentiating into insulin-producing cells . Bernat Soria and his colleagues at the Universidad Miguel Hernandez in San Juan, Alicante, Spain, added DNA containing part of the insulin gene to embryonic cells from mice. The insulin gene was linked to another gene that rendered the mice resistant to an antibiotic drug. By growing the cells in the presence of an antibiotic, only those cells that were activating the insulin promoter were able to survive. The cells were cloned and then cultured under varying conditions. Cells cultured in the presence of low concentrations of glucose differentiated and were able to respond to changes in glucose concentration by increasing insulin secretion nearly sevenfold. The researchers then implanted the cells into the spleens of diabetic mice and found that symptoms of diabetes were reversed.


Manfred Ruediger of Cardion, Inc., in Erkrath, Germany, is using the approach developed by Soria and his colleagues to develop insulin-producing human cells derived from embryonic stem cells. By using this method, the non-insulin-producing cells will be killed off and only insulin-producing cells should survive. This is important in ensuring that undifferentiated cells are not implanted that could give rise to tumors. However, some researchers believe that it will be important to engineer systems in which all the components of a functioning pancreatic islet are allowed to develop.

Recently Ron McKay and his colleagues described a series of experiments in which they induced mouse embryonic cells to differentiate into insulin-secreting structures that resembled pancreatic islets . McKay and his colleagues started with embryonic stem cells and let them form embryoid bodies—an aggregate of cells containing all three embryonic germ layers. They then selected a population of cells from the embryoid bodies that expressed the neural marker nestin (see Appendix B. Mouse Embryonic Stem Cells). Using a sophisticated five-stage culturing technique, the researchers were able to induce the cells to form islet-like clusters that resembled those found in native pancreatic islets. The cells responded to normal glucose concentrations by secreting insulin, although insulin amounts were lower than those secreted by normal islet cells (see Figure 7.2. Development of Insulin-Secreting Pancreatic-Like Cells From Mouse Embryonic Stem Cells). When the cells were injected into diabetic mice, they survived, although they did not reverse the symptoms of diabetes.


According to McKay, this system is unique in that the embryonic cells form a functioning pancreatic islet, complete with all the major cell types. The cells assemble into islet-like structures that contain another layer, which contains neurons and is similar to intact islets from the pancreas . Several research groups are trying to apply McKay's results with mice to induce human embryonic stem cells to differentiate into insulin-producing islets.

Recent research has also provided more evidence that human embryonic cells can develop into cells that can and do produce insulin. Last year, Melton, Nissim Benvinisty of the Hebrew University in Jerusalem, and Josef Itskovitz-Eldor of the Technion in Haifa, Israel, reported that human embryonic stem cells could be manipulated in culture to express the PDX-1 gene, a gene that controls insulin transcription . In these experiments, researchers cultured human embryonic stem cells and allowed them to spontaneously form embryoid bodies (clumps of embryonic stem cells composed of many types of cells from all three germ layers). The embryoid bodies were then treated with various growth factors, including nerve growth factor. The researchers found that both untreated embryoid bodies and those treated with nerve growth factor expressed PDX-1. Embryonic stem cells prior to formation of the aggregated embryoid bodies did not express PDX-1. Because expression of the PDX-1 gene is associated with the formation of beta islet cells, these results suggest that beta islet cells may be one of the cell types that spontaneously differentiate in the embryoid bodies. The researchers now think that nerve growth factor may be one of the key signals for inducing the differentiation of beta islet cells and can be exploited to direct differentiation in the laboratory. Complementing these findings is work done by Jon Odorico of the University of Wisconsin in Madison using human embryonic cells of the same source. In preliminary findings, he has shown that human embryonic stem cells can differentiate and express the insulin gene .

More recently, Itskovitz-Eldor and his Technion colleagues further characterized insulin-producing cells in embryoid bodies . The researchers found that embryonic stem cells that were allowed to spontaneously form embryoid bodies contained a significant percentage of cells that express insulin. Based on the binding of antibodies to the insulin protein, Itskovitz-Eldor estimates that 1 to 3 percent of the cells in embryoid bodies are insulin-producing beta-islet cells. The researchers also found that cells in the embryoid bodies express glut-2 and islet-specific glucokinase, genes important for beta cell function and insulin secretion. Although the researchers did not measure a time-dependent response to glucose, they did find that cells cultured in the presence of glucose secrete insulin into the culture medium. The researchers concluded that embryoid bodies contain a subset of cells that appear to function as beta cells and that the refining of culture conditions may soon yield a viable method for inducing the differentiation of beta cells and, possibly, pancreatic islets.

Taken together, these results indicate that the development of a human embryonic stem cell system that can be coaxed into differentiating into functioning insulin-producing islets may soon be possible.
Future Directions

Ultimately, type 1 diabetes may prove to be especially difficult to cure, because the cells are destroyed when the body's own immune system attacks and destroys them. This autoimmunity must be overcome if researchers hope to use transplanted cells to replace the damaged ones. Many researchers believe that at least initially, immunosuppressive therapy similar to that used in the Edmonton protocol will be beneficial. A potential advantage of embryonic cells is that, in theory, they could be engineered to express the appropriate genes that would allow them to escape or reduce detection by the immune system. Others have suggested that a technology should be developed to encapsulate or embed islet cells derived from islet stem or progenitor cells in a material that would allow small molecules such as insulin to pass through freely, but would not allow interactions between the islet cells and cells of the immune system. Such encapsulated cells could secrete insulin into the blood stream, but remain inaccessible to the immune system.

Before any cell-based therapy to treat diabetes makes it to the clinic, many safety issues must be addressed (see Chapter 10. Assessing Human Stem Cell Safety). A major consideration is whether any precursor or stem-like cells transplanted into the body might revert to a more pluripotent state and induce the formation of tumors. These risks would seemingly be lessened if fully differentiated cells are used in transplantation.

But before any kind of human islet-precursor cells can be used therapeutically, a renewable source of human stem cells must be developed. Although many progenitor cells have been identified in adult tissue, few of these cells can be cultured for multiple generations. Embryonic stem cells show the greatest promise for generating cell lines that will be free of contaminants and that can self renew. However, most researchers agree that until a therapeutically useful source of human islet cells is developed, all avenues of research should be exhaustively investigated, including both adult and embryonic sources of tissue.

Page citation: 7. Stem Cells and Diabetes . In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2006 [cited Monday, December 15, 2008] Available at <http://stemcells.nih.gov/info/scireport/chapter7>

Trachea Grown With Stem Cells

European doctors have successfully given a woman a new windpipe with tissue grown from her own stem cells.The ground-breaking procedure could revolutionise how doctors carry out organ transplants in the future.



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Doctors took wind pipe from a death women .They stripped all the cells in donors windpipe.they then took stem cells from patients Bone marrow,which is then used to create millions of cartilage and tissue cells to cover and line of the wind pipe.Surgeons then cut airways in size and in june 2008 they implaneted into patient .Scientist predict that this start of a new era where body organs are grown to order by using patients own stem cells and transplanted it without a risk of rejection

Adult Stem Cell & Regeneration Animation

Stem cell therapy for ALS

Besides to the use of bone marrow stem cells for treating hemotological malignancies, which is an established chemical practice today. Bone marrow cells is also under intense investigation for regenerating various organs such as heart, liver and lung .This particular study that will taking about today is " possibly of using bone marrow cells in treating a disease ALS is investigated ALS is a lethal condition associate with the degenration of Motor Neurons in the spinal cord,Cerbral cortex and brainstem.


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Actual cause of ALS is unknown. Although some ALS patients have a genetic mutation. Presently there is no cure for ALS The question of the study is.” whether bone marrow cells from healthy mice can inhibit the progression of disease in mouse model of ALS?"And subsequent question is do the stem cells cross the Blood-brain barrier? also total of such status canceled/what will attract with all possible way they for Mouse model which displays a predisposition and ALS like disease. The Mutated enzyme of human SOD1 ALS like carrying the GLY93 to alanine mutation is expressed in mouse, so that it mouse express pathology of Human ALS.Bonemarrow cells from the healthy mice are transferred to the mice with are predisposed to ALS.so the progress of ALS can be inhibited.

Kidney Function Animation

As everyone knows we have two kidneys, each functioning independently, Diuretic action occurs in the kidney this is where the body controls the fitration,reabsorption and excretion of water small molecules and ions such as sodium and potassium .Outer layer if the kidney is called cortex, and the inner layer is called Medulla which has millions of special structures called Nephrons.

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Fitration and Excretion in the Nephron
Nephron is a tubular structure similar to pores pipe,Glomerules is the starting point for the flow through the nephron.Blood enters to Glomerules through Afferent arteriole blood exits the Glomerules to efferent arteriole.the blood is filtered in Glomerules by osmosis and diffusion.

As blood passes through the porous capillary loops water and small molecules (50,000 molecular weight) are filtered passing it to the Bowmanns space, this creates the luminal fluid flowing through the nephron tubule .


  • About 1/5 of the total blood volume is continually filtered into the Bowmanns capsule.99% of this volume is reabsorb leaving only a small volume to be excreted as urine .
  • Each section of the nephron has a different morphology of cells making up the single cell wall, which causes differences in water permeability and ion transport.
  • First section of the nephron is called the proximal convoluted tubule; the proximal convoluted tubule is highly permeable.
  • Capillaries nearby the proximal convoluted tubule absorbs about 65% filtered sodium and water. Which was let out by tubule.
  • All diuretics called carbonic anhydrase inhibitors mostly act on this portion of the nephron.
  • Proximal convoluted tubule leads into the Henle loop, which has a thin descending limb and thin and thick ascending limb. The thick ascending limb normally reabsorbs about 25% of filtered sodium but does not allow water to reabsorb.
  • Sodium potassium chloride ion co-transporters are block by loop diuretics on the luminal membrane.
  • Next section is called Distal Convoluted tubule; this section doesn't allow water to reabsorb but reabsorbs sodium from sodium chloride ion co-transporters.
  • Thiazide diuretics act here on this transporter, the last section of the nephron is called collecting tubule. Sodium channel blockers and aldosterone antagonist diuretics act here.



Detail view
Re-absorption molecules
Each site on the nephron tubule, certain molecules are able to permeate the wall and leak out into the interstitium, these molecules will be reabsorb to the Para tubular capillary and will be returned to the systemic blood supply

Inside tubule
As tubule wall is made-up of single layer cells, water molecules flow through the tubule


Loop of Henle and Loop Diuretics
  • The sodium potassium ATPase transporter drives sodium reabsorption on the antiluminal membrane.
  • For every 3 Sodium ions moving out of the cell to the interstitium 2 Potassium ions move from the interstitium to the cell. This causes a deficit of the sodium within the cell. The sodium potassium chloride transporter on the luminal membrane of the cell makes up this deficit. This transporter moves 1 Sodium, 1 Potassium, and 2 Chloride ions from the lumen into the wall of the nephron.
  • Two potassium and chloride ions move down the concentration gradients to their respective channels.
  • The potassium returns to the lumen through a potassium channel. The chloride is removed to the interstitium through chloride channel. The net result is a continuing transport of 3 Sodium ions and 6 Chloride ions from the luminal fluid into the interstitium. This sodium is reabsorb into the circulation.
  • Because of the secretion of potassium a positive voltage is generated in the lumen resulting in re-absorption of possibly charged ions to the paracellulary Junction
  • Loop Diuretics -Blockage of Na+,K+,Cl- transporter
  • When the loop diuretics block the sodium potassium chloride transporter the sodium potassium exchange begins.
  • The sodium from the lumen cannot replace sodium deficit. This blocks the overall re-absorption of sodium from this site and the nephron.
  • The net result is greater excretion of sodium chloride potassium calcium and magnesium in the presence of the loop diuretics.


Distal Convoluted Tubule Thiazide diuretics
  • Transporters present in the distal convoluted tubule are slightly different than those described in the ascending limb. in the distal convoluted tubule the sodium chloride Co- transporter replaces the sodium deficit caused by the sodium potassium ATPase.
  • The chloride is reabsorb through chloride channels and the potassium returns to the interstitium through potassium channel.

Distal Convoluted Tubules
However the thiazide diuretics bind that the chloride binding site and block the sodium chloride Co. transporter. This blocks sodium and chloride re-absorption resulting in next excretion of sodium and chloride.

Collecting Tubule sodium channels inhibitors (Na+)

Transporters present in the collecting tubules are slightly different than at the other sites of the nephron, sodium potassium exchange occurs on anti-luminal membrane, however the sodium is replaced at this site are the sodium channels on the luminal membrane and potassium excretion is completed by transport through potassium channels on the luminal membrane. this continuing exchange results in overall sodium re-absorption and potassium excretion .

When the sodium channel inhibitors are present they block the sodium channel, this prevents the continual re-absorption of sodium and also prevents the overall excretion of potassium this is why sodium channel inhibitors are called potassium sparing.
Thus all the diuretic agents described directly decrease the re-absorption of sodium by blocking specific ion transporters in the various segments of the nephron tubule this indirectly affects re-absorption and excretion of water and other ions as described for each type of diuretic

Sepsis

Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) caused by infection.The body may develop this inflammatory response to microbes in the blood. The related layman's term is blood poisoning.Symptoms related to the provoking infection, sepsis is characterized by evidence of acute inflammation present throughout the entire body, and is therefore frequently associated with fever and elevated white blood cell count (leukocytosis)or low white blood cell count and lower than average temperature. The modern concept of sepsis is that the host's immune response to the infection causes most of the symptoms of sepsis, resulting in hemodynamic consequences and damage to organs. This host response has been termed systemic inflammatory response syndrome (SIRS) and is characterized by hemodynamic compromise and resultant metabolic derangement.
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When a microbe infects a tissue, the cascades of pro-inflammatory mediators are released, but these are counterbalanced by the release of anti-inflammatory agents. This balance enables mobilization of defense and microbe killing mediators, while allowing tissue repair and healing. In sepsis this equilibrium in perturbed, and pro inflammatory mediators and dominate to illustrate endothelial damage. Studies at the extent of coagulation and fibrinosios abnormalities in sepsis have shown that endothelial damage promotes coagulation normally modulators promote fibrinosios to contract thrombosis. In sepsis however they endothelial damage is proposed to suppress fibrinolysis, further contributing to the loss of control .As the body tries to return to a normal state endogenous modulators of homeostasis are consumed and their levels become low .In parallel to endothelial damage promotes further inflammation. Left unopposed the endothelial damage accumulates and coagulation. This cycle of uncontrolled inflammation and coagulation deals with the progression of sepsis resulting hypoxia and ischemia organ dysfunction and ultimately death or a large number of patients

Cell Mediated Immune Response

Cell-mediated immunity is an immune response that does not involve antibodies or complement but rather involves the activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. Historically, the immune system was separated into two branches: humoral immunity, for which the protective function of immunization could be found in the humor (cell-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was associated with cells. CD4 cells or helper T cells provide protection against different pathogens.


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Cellular immunity protects the body by:
1. activating antigen-specific cytotoxic T-lymphocytes that are able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens;
2. activating macrophages and natural killer cells, enabling them to destroy intracellular pathogens; and
3. stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses.
Cell-mediated immunity is directed primarily at microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in removing virus-infected cells, but also participates in defending against fungi, protozoans, cancers, and intracellular bacteria. It also plays a major role in transplant rejection.

Lecture on Vaccines and HIV Evolution

Lecture was giver by Dr.Bruce.D.Walker from Howard Hughes Medical Institute,Topic is Vaccines and HIV Evolution.some of important points from the lecture.About 33 million people are currently infected by HIVof this 90% of people are living in Developing countries

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How vaccine works

  • Preventing infection (sterilizing immunity).
  • Prevent disease (but doesn't prevent infection) by keeping the microbe or its toxins in check (non-sterilizing immunity).
  • Goal of the vaccine is to alleviate symptoms and stem transmission.


When B-cells exposed to pathogen are converted into plasma cell and starts to secreate antibodies who job is directly neutralizes virus by binding to outer surface of the virus cell.

Aim of vaccine is to trick the B-cells in thinking that are seeing pathogen,so that they start making antibodies that will prevent future infection.

Possible vaccine
  • Killed Virus
  • Live attenuated Virus
  • Recombinant protein
  • Recombinant Virus

Reasons for non availability HIV vaccine

  • HIV Reverse trascriptase makes frequent errors during replication
  • Sequence variation leads to escape from antibodies and CTL(cytotoxic T-cells) responses
  • Loss of CD4 cells leaves immune system unable to respond effectively to newly emerging Mutants.
  • GP120 envelope protein undergoes lot of mutation which in turn makes the gp120 structure differnt,Because of this antibodies are unable to bind with HIV virus.

Hiv Vaccine Marveck
On 21 September 2007, the pharmaceutical giant Merck called a halt to a phase II trial of a new vaccine candidate against HIV . An interim assessment showed that the vaccine, long considered the most promising in development, failed both in preventing HIV infection and in reducing the viral load of those infected.The vaccine candidate (Merck V520) is a mixture of three components, each a weakened adenovirus vector carrying one of the three synthetic HIV genes gag, pol and nef. The vaccine is designed to elicit a cell-mediated immune response, to stimulate the body’s own CD8 T-cells that recognize and kill the HIV-infected cells.

http://www.i-sis.org.uk/NewstrategyHIVvaccine.php

Biomolecular Simulation Lecture

Lecture is Titled New architecture for New Biology Horizon,it talks about algorithms ,simulations involved proteomic studies especially molecular dynamics.this talks is view point of computer scientist who involved in creating alogrithms for biological sciences.so this lecture will very useful for bioinformaticians who are intersted in scripting.

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This talk describes the current state of the art in biomolecular simulation and explore the potential role of high-performance computing technologies in extending current capabilities.



The lecture starts with introduction about biochemistry and different types of protein structures (primary secondary,tertiary ).Talks about constraints in developing a three-dimensional structure(eventhough we know all amino acid structures) like identifying the fold region,binding region of proteins.

Next speaker talks about Molecular dynamics and its various algorithms involved in it.