December 17, 2009

New issue of main scientific Journal of Ecuador

Our research team published a brief review on Stem Cells. It was published in Spanish for our collegues in Latin America. I hope it will be useful in the daily practice of medicine, below you can find the link.

Scientific Report: Stem cells: definitions and conceptual approach



Journal of the Faculty of Medical Sciences
Revista de la Facultad de Ciencias Médicas
Volume 34, Nº1-2, year 2009
Central University of Ecuador
Universidad Central del Ecuador
Sodiro N14-121 e Iquique
Quito-Ecuador
rev.fac.ccmm.quito@fcm.uce.edu.ec
Copyright © 2009

Indexed by:
LILACS – BIREME: Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Centro Latinoamericano y del Caribe de Información en Ciencias
LATINDEX: Sistema Regional de Información en Línea para Revistas Científicas de América Latina, el Caribe, España
IMBIOMED: Indice Mexicano de Revistas Biomédicas Latinoamericanas

Editorial
-Diabetes Mellitus and Depression
-Assurance and Quality
Research Reports
-Depression as a risk factor for inadequate glycemic control in patients with Diabetes Mellitus.
-Pulmonary embolism by Angiotomography (AngioTC): study two diagnostic centers in the city of Quito.
-Colonization of sinks with Pseudomonas aeruginosa in neonatal units and intensive care at a hospital in Cajamarca – Perú.
-Neurological outcome in patients with severe traumatic brain injury, according to the jugular vein saturation
-Hematological reference values in Ecuadorian Andean population, using analyzer Sysmex XE-2100®.
-Skin rash in a patient woman with hairy cell leukemia
-Dengue fever associated with acalculous cholecystitis
News
-New indexes of the Journal of the Faculty of Medical Sciences
-Human pentavalent vaccine will be developed in Ecuador
-National Transplant Organism (ONTOT) and transplant activities in the country
-Ecuadorian Society of Palliative Care: first year of activities
Special Article
Darwin and Modern Medicine
Public Health
Declaration on ethics and the use of evidence scientific and clinical practice guidelines to improve the quality of healthcare services: the Declaration of Heredia
Images in Medicine
Neurofibromatosis type I
Education
Informed Consent in Anesthesiology - Part II: The doctor-patient basis of informed consent

August 21, 2009

The DNA of Nicolaus Copernicus

Nicolaus Copernicus (19 February 1473 – 24 May 1543) was the first astronomer to formulate a comprehensive heliocentric cosmology, which displaced the Earth from the center of the universe. His epochal book, De revolutionibus orbium coelestium (On the Revolutions of the Celestial Spheres), published in 1543 just before his death, is often regarded as the starting point of modern astronomy and the defining epiphany that began the scientific revolution.

Copernicus was a mathematician, astronomer, physician, quadrilingual polyglot, classical scholar, translator, artist, Catholic cleric, jurist, governor, military leader, diplomat and economist. Among his many responsibilities, astronomy figured as little more than an avocation — yet it was in that field that he made his mark upon the world.


Recently, Bogdanowicz W et al described the findings of the DNA analysis of the human remains of Copernicus: Bogdanowicz W, Allen M, Branicki W, Lembring M, Gajewska M, Kupiec T. Genetic identification of putative remains of the famous astronomer Nicolaus Copernicus. Proc Natl Acad Sci U S A. 2009 Jul 28; 106(30):12279-82.

An identical HVI and HVII mtDNA profile [with the polymorphisms:16129A; 16316G; 263G; 315.1C. In addition to the hypervariable region analysis, 16 haplogroup informative SNP positions were examined (709G, 1719G, 1811A, 3010G, 6365T, 6776T, 7028C, 8251G, 8697G, 9055G, 11251A, 12372G, 13708G, 14766C, 14798T, and 15904C). Analysis of these haplogroup informative mtDNA polymorphisms indicates that the examined individual belongs to haplogroup H, which is the most frequent of the 6 European-specific haplogroups.

Copernicus’ maternal lineage may have originated from Silesia, and can thus be of German descent. Copernicus’ grandmother, Catherina, was first married to Heinrich Peckau, who was a member of the council of Thorun. After Heinrich’s death, Catherina was married to a trader and famous enemy of the Teutonic Knights—Lucas Watzenrode. Together they had 3 children, Christina, Lucas, and Nicolaus Copernicus’ mother, Barbara.



Autosomal STR genotyping results were D8S1179 11/14; D3S1358 16/ 18; TH01 9.3/9.3; D19S433 13/13; VWA 14/15; D5S818 12/12. Y-Chromosome genotyping: DYS456– 16; DYS389I– 13; DYS390– 23;DYS389II– 29; DYS458– 19; DYS19– 14; DYS385– 11, 13; DYS393– 13; DYS391– 11; DYS439– 12; DYS635– 23; DYS392– 13; Y GATA H4– 12; DYS437– 15; DYS438– 12; DYS448– 19. This haplotype has been found in individuals from many countries, including Austria, Germany, Poland, and the Czech Republic. It is interesting to note that Copernicus’ paternal ancestors may also have originated from Silesia. Copernicus’ father, also named Nicolaus, was a known trader in Cracow. He moved to Thorun in 1458 where he married Barbara Watzenrode. Nicolaus Copernicus was their youngest son. The Y-chromosome data that we obtained will be useful if reference samples from some of Copernicus’ relatives along the paternal lineage are ever collected.

The SNP position rs12913832, located in an evolutionarily conserved region within intron 86 of the HERC2 gene, revealed a homozygous C/C genotype which is the predominant genotype among blue or gray-eyed humans (~80%). The result indicates that Copernicus might have had light iris color, a finding that is rather unexpected given that he is usually shown in portraits with dark eyes.

The authors concluded that:
“Taking all data into consideration, i.e., the identical genetical profiles in the skeletal remains and reference hairs along with the other anthropological and archeological information, they concluded that the skeletal remains derived from the St. Cross Altar tomb at Frombork Cathedral are those of the great Polish astronomer, Nicolaus Copernicus”.

May 3, 2009

iPS cells and ALS

Human induced pluripotent stem cells (iPS cells) and Amyotrophic Lateral Sclerosis (ALS)

Researchers reported a milestone experiment in July of 2008, using a new method, one that doesn't require embryos at all, to generate the first motor neurons from stem cells in two elderly women with Lou Gehrig's disease, or ALS. Led by Kevin Eggan at the Harvard Stem Cell Institute and Christopher Henderson at Columbia University, the research team reported that they had generated motor neurons from the skin cells of two elderly patients with a rare form of ALS, or Lou Gehrig's disease, a progressive neurodegenerative condition. The new study marks an important first step on the road toward real stem-cell-based therapies, and also answers several plaguing questions about the pioneering stem-cell technique known as induced pluripotent stem cell, or iPS, generation.
Dimos J, Rodolfa K, Niakan K, Eggan K et al. Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons. Science Express, Science, 29 August 2008, 321 ( 5893): 1218 – 1221. DOI: 10.1126/science.1158799
The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell types affected by that patient's disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. We have generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.
The technique was primarily developed by Kyoto University scientist Shinya Yamanaka in 2006, involves reprogramming a patient's ordinary skin cells to behave like stem cells, then coaxing them into the desired tissue-specific cells. Using the motor neurons created from ALS patients, scientists can now study the progress of the disease as the affected cells develop, degenerate and die in a dish , something researchers could never do before for such slow-moving conditions. Once scientists understand the development of ALS, they may be able to create more effective treatments, or perhaps even a cure. Yamanaka in 2007 showed that the introduction of four genes into an adult human skin cell could reprogram it back to an embryonic state, he also had reported the same achievement in mice. Like embryonic stem cells, these reprogrammed adult cells could be coaxed into becoming any other type of cell : from skin to nerve to muscle. But researchers questioned whether the new stem cells would behave as predictably or as safely as embryonic stem cells, or whether iPS would consistently yield usable cells.
Cell 126, 663–676, August 25, 2006. DOI 10.1016/j.cell.2006.07.024
Takahashi K and Yamanaka S. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors.
Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.



Researchers questioned whether iPS would work with delicate cells from older people or with cells taken from patients with disease. Yamanaka used skin cells from healthy middle-aged people in his study. Eggan and Henderson tackled both issues at once, by working with cells from two siblings, ages 82 and 89, who both had ALS. It turned out that generating iPS cells from older patients proved no more difficult than growing them from younger ones. In the lab, they successfully turned stem cells into motor neurons, the cells that connect the spinal cord to the body's muscles and which degenerate in ALS. But researchers have not been able to prove that these cells will be clinically useful, that is, whether the new nerve cells will work as well as healthy ones in the spinal cord of a patient. Testing the viability of cells made from iPS stem cells is still a long way off, mostly because iPS requires the use of viruses to deliver the time (reversing genes into adult cells) that works in the lab, but it is not yet safe for patients.
To use iPS cells in patients, researchers would have to find a way to reprogram adult cells using chemicals, rather than genes.

April 4, 2009

Identical twins and Forensic Genetics

The main interest of Forensic scientist is to establish minimal differences between two individuals. The unique situation in which we cannot conclude this is in the case of identical twins or monozygotic twins. There are two types of twins: fraternal and identical. Fraternal, or dizygotic, twins are different in their genetic make-up whereas identical, or monozygotic, twins are genetically the same. Monozygotic twins develop from the same ovum, are always the same sex and share identical genetic information. They also tend to be alike in both physical and mental characteristics. Furthermore, in the last years a few cases published in the media have shown this conflict on the DNA application in the Court. With identical twins, even if you sequenced their whole genome you would not find differences, they are practically clones. There is simply no test that explains the difference between two identical twins, at least for now.

The cases are:

Case 1: Two years ago, identical twin brothers Raymon and Richard Miller both had sex with the same woman who became pregnant. In May 2007, the judge decided that Raymon is the legal father of the child although the DNA paternity test couldn’t provide definitive proof, and the child support was split between the two brothers.
Who's Your Daddy? Paternity Battle Between BrothersJudge Uses Old-Fashioned Detective Work to Determine Who the Father Is... When the paternity test came back with the same results, he took the matter to the courts where Judge ruled that even in light of the identical DNA tests and overlapping relationships, Raymon would remain the legal father of the child. Raymon hopes to continue appealing the decision. In Missouri, a paternity test must come back with 98 percent or higher probability that DNA matches in order for a man to be named the legal father.
Case 2: In February, millions of dollars worth of jewelry was stolen in Berlin. Two of the suspects are identical (monozygotic) twins, Hassan and Abbas O. DNA analysis showed that one or both of them were probably at the scene of the crime but it’s impossible to tell. If only one of the brothers is guilty, investigators can’t tell for sure which one it is.
Berlin's Massive Jewelry Heist
Perfect Genes for a Robbery - Investigations into the spectacular heist at Berlin's luxury department store KaDeWe have run into a problem: The suspected robbers may be identical twins. That means that the traces of DNA found at the crime scene could be useless under German law. Investigators identified the brothers using clearly identifiable traces of DNA from a glove found at the scene of the crime, according to police… Then there's the fact that the DNA, which ordinarily would serve as powerful evidence, may prove worthless in obtaining convictions for the KaDeWe case. It is impossible to distinguish between the DNA of identical twins using the kind of genetic analysis typically used in law enforcement,... German law limits the amount of genetic analysis that can be carried out by investigators.
Case 3: In Malaysia, investigators were unable to figure out which one of a pair of identical twins trafficked 166 kilograms of cannabis and 1.7 kilograms of opium. A judge dismissed the case and both twins were set free.
Identical twin escapes hanging in Malaysia after judge fails to tell brothers apart. An identical twin has escaped execution in Malaysia after a judge ruled it was impossible to determine which brother was the drug trafficker. The twins wept and embraced after judge dismissed the case. According to the judge there was no doubt that either Sathis Raj or Sabarish Raj, both 27 years old, was guilty of trafficking 166 kilograms of cannabis and 1.7 kilograms of opium, but because they looked the same and had the same DNA it was impossible to determine which one.
In reality, identical twins do not have perfectly identical DNA due to epigenomic chemical modifications and DNA copy number variations.


Epigenomic chemical modifications
Human monozygotic (MZ) twins occur in about 1 in 250 live births. Since they are derived from a single zygote, they are considered genetically identical. However, discordance is well known for many phenotypic traits and diseases. This discordance is typically attributed to differences in placenta, amniotic sac and vascularization of separate cell masses or even mosaicism in their genetic and cytogenetic composition. Epigenetic factors that influence expression of genes represent another potential difference that could explain phenotypic discordance between MZ twins. There are 2 major classes of epigenetic alterations of genes: methylations of cytosine at cytosine-guanine (CpG) dinucleotides and acetylations and methylations of DNA bound histones. Cytosine methylation at regions of gene promoters rich in CpG dinulceotides usually silences genes, whereas histone acetylation is frequently associated with activation of genes.
The largest twin study on epigenetic profiles yet reveals the extent to which lifestyle and age can impact gene expression, an international research team reports in PNAS journal. Senior author Manel Esteller of the Spanish National Cancer Center in Madrid and colleagues found that 35% of twin pairs had significant differences in DNA methylation and histone modification profiles. DNA methylation can be caused by environmental exposures, such as diet and physical activity.
Methylation can lead to differences in gene expression and as we age, the amount of DNA methylation increases.
DNA copy-number-variation profilesAnother way in which the genomes of identical twins may differ is in copy number variation (CNV) that appears as segments of DNA that are missing, occur in multiple copies, or have flipped orientation in the genome. Identical (monozygotic) twins have been found to have different CNVs which could explain why even identical twins are not truly identical in appearance or other physical characteristics despite similar environmental exposures. For example, one twin sometimes develops a disease while the other does not.

March 31, 2009

The Romanovs Decoded

This is a great job of three teams of scientists, leading by: Peter Gill et al, Eugeny Rogaev et al. and Michael D. Coble, respectively. Nice work, collegues!
The story of Last Russian Royal Family is closing, finally. I reproduce part of the information here.
In July 1991, nine bodies were exhumed from a shallow grave just outside Ekaterinburg, Russia. Circumstantial evidence, along with mitochondrial DNA sequencing and matches, gave strong evidence to the remains being those of the Romanovs, the last Russian Royals who were executed on July 18, 1918. This first analysis was made by Peter Gill and his team in UK (Central Research and Support Establishment, Forensic Science Service, Aldermaston, Reading, Berkshire, UK).
Nine skeletons found in a shallow grave in Ekaterinburg, Russia, in July 1991, were tentatively identified by Russian forensic authorities as the remains of the last Tsar, Tsarina, three of their five children, the Royal Physician and three servants. We have performed DNA based sex testing and short tandem repeat (STR) analysis and confirm that a family group was present in the grave. Analysis of mitochondrial (mt) DNA reveals an exact sequence match between the putative Tsarina and the three children with a living maternal relative. Amplified mtDNA extracted from the remains of the putative Tsar has been cloned to demonstrate heteroplasmyat a single base within the mtDNA control region. One of these sequences matches two living maternal relatives of the Tsar. We conclude that the DNA evidence supports the hypothesis that the remains are those of the Romanov family.
Reference: Gill P, Ivanov PL, Kimpton C, Piercy R, Benson N, Tully G, Evett I, Hagelberg E, Sullivan K. Identification of the remains of the Romanov family by DNA analysis. Nat Genet. 1994 Feb;6(2):130-5.

The following sequences for Tsar Nicholas II, his cousin, Count Nicholai Trubetskoy, Tsarina Alexandra, and Prince Philip, the Duke of Edinburgh, are taken from:
Reference: Bryan Sykes book, "The Seven Daughters of Eve."

Tsar Nicholas Romanov, Haplotype T, mt DNA Sequence: 16126C, 16169Y*, 16294T, 16296T - 73G, 263G, 315.1C
Count Trubetskoy, Haplotype T, mt DNA Sequence: 16126C, 16169Y, 16294T, 16296T - 73G, 263G, 315.1C
*The Tsar's sequence contains a new mutation at position 169, a state referred to as heteroplasmy - the existence of more than one mitochondrial type in the cells of an individual, i.e., the presence of both normal and mutant mtDNA in a single individual. The remains of his brother, Grand Duke of Russia, Georgij Romanov were exhumed, and the results were identical to the Tsar's,including the heteroplasmy at 16169Y. Mitosearch: DQR2R
Tsarina Alexandra, Haplotype T, mt DNA Sequence: 16111T, 16357C - 263G, 315.1C
Prince Philip, Haplotype T, mt DNA Sequence: 16111T, 16357C - 263G, 315.1C
Tsarina Alexandra, the three children buried with her, and Prince Philip's mitochondrial DNA were an exact match on 740 tested nucleotides. Mitosearch: 2ZACX

Czar Nicholas II, his wife Alexandra and their five children were assassinated as civil war broke out; numerous stories circulated over the years that Anastasia, then 17, somehow escaped. In 1991, five bodies were found and later identified as the Romanovs. Independent studies done in the US and England and later by Rogaev compared extracted DNA samples to those from descendents of the royal family. Two bodies, however, were missing, leaving some question as to the fate of two of the czar's children. Bone fragments were found in the summer of 2007, not far from the original discovery site, about 900 miles east of Moscow, but had been badly damaged by not only time and natural decomposition, but also by acid and fire, as the murderers apparently sought to fully destroy the bodies and evidence of the murder.

In 1890–1891 Nicholas II, then-heir to the throne was on an around-the-world voyage. On 11 May 1891, during his visit to Osaka, Japan, he was attacked and injured in an apparent assassination attempt. The escort policemen swung at Nicholas II’s head with a saber; however the following blow was parried by Prince George of Greece and Denmark who was accompanying Nicholas II. Although the wound was not life-threatening, Nicholas II was severely bleeding and a long scar remained on the right side of his forehead. The Y-chromosome haplotype of the Tsar appears to belong to haplogroup R1b.

Reference: Evgeny I. Rogaev, Anastasia P. Grigorenko, Yuri K. Moliaka, Gulnaz Faskhutdinova, Andrey Goltsov, Arlene Lahti, Curtis Hildebrandt, Ellen L. W. Kittler, and Irina Morozova. Genomic identification in the historical case of the Nicholas II royal family. PNAS 2009 : 0811190106v1-pnas.0811190106.

Reference: Coble MD, Loreille OM, Wadhams MJ, Edson SM, Maynard K, et al. (2009) Mystery Solved: The Identification of the Two Missing Romanov Children Using DNA Analysis. PLoS ONE 4(3): e4838. doi:10.1371/journal.pone.0004838
Accurate unambiguous identification of ancient or historical specimens can potentially be achieved by DNA analysis. The controversy surrounding the fate of the last Russian Emperor, Nicholas II, and his family has persisted, in part, because the bodies of 2 children, Prince Alexei and 1 of his sisters, have not been found. A grave discovered in 1991 contained remains putatively identified as those of the Russian Royal family. However, not all family members were represented. Here, we report the results of genomic analyses of new specimens, the human remains of 2 burned skeletons exhumed from a grave discovered in July 2007, and the results of a comprehensive genomic analysis of remains from the 1991 discovery. Additionally, ≈117 years old archival blood specimens from Nicholas II were obtained and genotyped, which provided critical material for the specific determination of individual identities and kinship identifications. Results of genotypic analyses of damaged historical specimens were evaluated alongside samples from descendants of both paternal and maternal lineages of the European Royal families, and the results conclusively demonstrate that the recently found remains belong to children of Nicholas II: Prince Alexei and his sister. The results of our studies provide unequivocal evidence that the remains of Nicholas II and his entire family, including all 5 children, have been identified. We demonstrate that convergent analysis of complete mitochondrial genome sequences combined with nuclear DNA profiles is an efficient and conclusive method for individual and kinship identification of specimens obtained from old historic relics.

One of the greatest mysteries for most of the twentieth century was the fate of the Romanov family, the last Russian monarchy. Following the abdication of Tsar Nicholas II, he and his wife, Alexandra, and their five children were eventually exiled to the city of Yekaterinburg. The family, along with four loyal members of their staff, was held captive by members of the Ural Soviet. According to historical reports, in the early morning hours of July 17, 1918 the entire family along with four loyal members of their staff was executed by a firing squad. After a failed attempt to dispose of the remains in an abandoned mine shaft, the bodies were transported to an open field only a few kilometers from the mine shaft. Nine members of the group were buried in one mass grave while two of the children were buried in a separate grave. With the official discovery of the larger mass grave in 1991, and subsequent DNA testing to confirm the identities of the Tsar, the Tsarina, and three of their daughters – doubt persisted that these remains were in fact those of the Romanov family. In the summer of 2007, a group of amateur archeologists discovered a collection of remains from the second grave approximately 70 meters from the larger grave. We report forensic DNA testing on the remains discovered in 2007 using mitochondrial DNA (mtDNA), autosomal STR, and Y- STR testing. Combined with additional DNA testing of material from the 1991 grave, we have virtually irrefutable evidence that the two individuals recovered from the 2007 grave are the two missing children of the Romanov family: the Tsarevich Alexei and one of his sisters.

Well. I guess this is the end of the story… at least for now.

March 22, 2009

Genes and Alzheimer's disease

Alzheimer's disease is the most common form of dementia. Medical research has identified four genes that influence disease development. Three of these genes affect younger people, and one affects older people. Early onset Alzheimer's disease. The three genes that have a major effect on risk of Alzheimer's disease are the amyloid precursor protein (APP) gene and two presenilin genes (PSEN-1 and PSEN-2). People with any of these genes tend to develop the disease in their 30s or 40s, and come from families in which several members also have early onset Alzheimer's disease.
The prevalence of these genes is as follows:
A small number of families worldwide have a genetic fault on chromosome 21 in the APP gene, which affects production of the protein amyloid.
Amyloid build-up in the brain has been linked to Alzheimer's disease.
A slightly larger number of families carry a fault on chromosome 14 (PSEN-1) causing early onset familial Alzheimer's disease. A very small group of families (mainly in the United States) has a fault on chromosome 1 (PSEN-2), causing early onset familial Alzheimer's disease. The important thing to remember is that all of these risk genes are very rare in the population. Indeed, they account for less than one in 1000 cases of Alzheimer's disease.
On average, half of the children of a person with one of these rare genetic defects will inherit the disease. Probably all those who inherit the genetic defect develop Alzheimer's disease at a comparatively early age. People who do not inherit the disease cannot pass it on.If you have two or more close relatives (a close relative is defined as a parent, brother or sister) who developed Alzheimer's disease before the age of 60, your GP could advise you about genetic counselling and testing and refer you to a geneticist, if appropriate.
Late onset Alzheimer's disease occurs over the age of 65 and is the most common form of Alzheimer's disease, accounting for over 99 per cent of cases. Currently, only one gene is known to influence disease development: apolipoprotein E (APOE). The effects of the APOE gene appear more subtle than the genes affecting early onset Alzheimer's, and even individuals with two copies of the risky form of the gene are not certain to develop Alzheimer's disease. This gene comes in three forms: APOE2, APOE3, APOE4. We all have two copies of the gene, and these may be the same as each other or different.
APOE4 is associated with a higher risk of Alzheimer's. About a quarter of the population inherits one copy of the APOE4 gene. This increases their risk of developing Alzheimer's disease by up to four times. • Two per cent (2%) of the population gets a 'double dose' of the APOE4 gene -one from each parent, which increases the risk of developing Alzheimer's disease by about ten times. • Sixty per cent (60%) of the population has a 'double dose' of the APOE3 gene and is at 'average risk'. About half of this group develops Alzheimer's disease by their late 80s.
The APOE2 form of the gene is mildly protective against the development of Alzheimer's disease. Eleven per cent of the population has one copy of APOE2 together with a copy of APOE3, and one in 200 has two copies of APOE2. Some researchers think that APOE4 does not affect whether a person will get the disease but when they get it. This means that people with APOE4 develop the disease before people with APOE2.
There are more genes influencing the risk of developing Alzheimer's disease that still remain to be found. Recent scientific developments allow researchers to test every gene in the human genome for a relationship with Alzheimer's disease. We anticipate new discoveries of susceptibility genes in the next few years.
Vascular dementia is the second most common form of dementia. There are a number of very rare forms of the disease that are caused by genetic mutations. For example, mutations in a gene called Notch3 result in a form of vascular dementia known as cerebral automsomal dominant arteriopathy with subcortical infarcts and leukoencephalopahth (CADASIL). Variation in the APP gene, which also contains variants responsible for rare cases of Alzheimer's disease, leads to a form of vascular dementia called heritable cerebral haemorrhage with amyloidosis (HCHWA). However, it is important to remember that these forms of the disease are very rare. There are no established direct genetic causes for the more common forms of vascular dementia, but the APOE gene (described above) is a risk factor for vascular dementia as well as for Alzheimer's disease. There are known genes that contribute to some of the risk factors for vascular dementia, such as high cholesterol levels, high blood pressure and diabetes. People with Down's syndrome are at particular risk of developing Alzheimer's disease. Different studies have suggested different rates of dementia among people with Down's syndrome, but it could be as high as 50 per cent of people with Down's syndrome in their 60s.
Huntington's disease is a progressive hereditary disease caused by a particular gene. The course of the disease varies for each person, and dementia can occur at any stage. Some other forms of dementia can be inherited. Some people with fronto-temporal dementia (such as Pick's disease), or with Creutzfeldt-Jakob disease and similar conditions have a very strong family history of the disease. In some of these cases the genetic link has been found. For example, some families with inherited fronto-temporal dementia have one of a number of faults on the tau gene. However, these inherited forms of dementia are rare.
Genetic testing - either for family members or for whole populations - is not a straight forward issue. Individuals need to think carefully before deciding to take a genetic test. The experience might be very difficult emotionally, may not provide conclusive results either way, and may cause practical difficulties. On the positive side, genetic testing might: identify people who might benefit from drugs used to treat Alzheimer's disease; help genetic researchers understand the disease better and so lead to improved treatment; help people to plan for the future.
However, it may create problems, for the following reasons: A genetic defect cannot be repaired, and effective treatment is not yet generally available, so a test might raise anxiety without offering a clear course of action; the genetic test for a higher risk of late onset Alzheimer's disease (APOE4) cannot accurately predict who will develop the disease. Testing positive does not mean a person will definitely develop the disease, while testing negative does not guarantee that they will not. People testing positive could face discrimination affecting their ability to buy property, get insurance or plan financially for their old age, although there is a moratorium on the use of genetic information by insurance companies
Gene 'has key schizophrenia role'
Two studies have pinpointed a single gene as key to the development and treatment of schizophrenia. A US team from the Howard Hughes Medical Institute found that a mutated version of the DISC1 gene disrupts the growth and development of brain cells. And a team from the University of Edinburgh showed that the gene affects how patients respond to treatment.
DISC1 Gene. Linked in the early 1990s to mental illnesses prevalent in a large Scottish family. Over five generations many family members had developed schizophrenia, bipolar disorder, and other mood disorders. Each family member diagnosed with mental illness also carried a mutated copy of DISC1. The condition is a common form of mental illness, affecting up to 1% of adults worldwide. Several researchers showed that DISC1 plays a key role in normal brain development and the growth of individual neurons. However, carrying the wrong version of the gene can make this process go awry. Working on mice, they showed that DISC1 was active, both in cells taken from embryos and in brain stem cells taken from adult mice. When DISC1 levels were reduced in adult mice their brain cells failed to divide, and the animals developed symptoms mimicking schizophrenia in humans.
Further tests showed that DISC1 acts like lithium, a drug commonly prescribed as mood stabiliser to patients with mental illness, inhibiting the action of a key chemical in the brain. When mice with depressed levels of DISC1 were treated with this chemical, their symptoms began to improve.

March 14, 2009

Darwin and Galápagos: 200 years after

This year we celebrate two hundred years of the birth of Charles Darwin, and independently of this date, we celebrate the evolution’s theory and the Galápagos Islands, in my original country Ecuador.
Charles Robert Darwin (Naturalist, 1809 -1882) was born on February 12, 1809 in Shrewsbury, England. Darwin was born on the same day as Abraham Lincoln. He was the fifth child and second son of Robert Waring Darwin and Susannah Wedgwood. Darwin was the British naturalist who became famous for his theories of evolution and natural selection. Like several scientists before him, Darwin believed all the life on earth evolved (developed gradually) over millions of years from a few common ancestors.
From 1831 to 1836 Darwin served as naturalist aboard the H.M.S. Beagle on a British science expedition around the world. In South America, Darwin found fossils of extinct animals that were similar to modern species. On the Galápagos Islands in the Pacific Ocean he noticed many variations among plants and animals of the same general type as those in South America. The expedition visited places around the world, and Darwin studied plants and animals everywhere he went, collecting specimens for further study. The Darwin’s birds are very famous: Darwin’s Finches, The Mangrove finch, Galapagos Penguin, Galapagos Petrel, Albatros, Cucuves, Cucuve de Floreana.
Upon his return to London Darwin conducted thorough research of his notes and specimens. Out of this study grew several related theories: one, evolution did occur; two, evolutionary change was gradual, requiring thousands to millions of years; three, the primary mechanism for evolution was a process called natural selection; and four, the millions of species alive today arose from a single original life form through a branching process called speciation.

Darwin's theory of evolutionary selection hold
s that variation within species occurs randomly and that the survival or extinction of each organism is determined by that organism's ability to adapt to its environment. He set these theories forth in his book called, On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life (1859) or “The Origin of Species” for short. After publication of Origin of Species, Darwin continued to write on botany, geology, and zoology until his death in 1882. He is buried in Westminster Abbey.
Darwin wrote several famous texts about science: The Origin of Species, Voyage of the Beagle, The Descent of Man, The Autobiography, Charles Darwin's Letters: A Selection, 1825-1859.There is much to discuss and much to talk about the impact and development of evolution in science, religion and everyday life. Many authors have written books on this vast subject. It is not my purpose to do an extensive discussion on evoliucion but just remember this ingenious thinker.

Galápagos, Darwin and the birds
The Galápagos Islands are located at the equator and about 1,000 km off the coast of Ecuador in the Pacific. Galápagos comprises 14 major islands, more than 120 smaller islets and rocks, and the ocean around them. The total land mass is about 8000 km2 and the Galapagos Marine Reserve that surrounds the archipelago is 138,000 km2. The islands have a current length of less than 4 million, and separately from other land masses as a result of volcanic eruptions. 
People, both residents and tourists, have become part of the ecosystem of the Galapagos, as many species of flora and fauna that were introduced into the islands by humans. The challenge of everyone is to protect and conserve Galápagos and found the best way to integrate the needs of the human population with ecosystem, limiting the biological impact in this unique part of the world. It’s not possible separate the environmental sustainability of economic and social.
The Galapagos Islands and Marine Reserve contains a unique combination of ocean and terrestrial ecosystems, each with many different habitats and communities. They are located at the point where ocean currents are important, and the islands include the intersections between several tectonic plates in motion. The combination of these circumstances makes it an unparalleled location on the planet. The archipelago is also the best preserved tropical ocean in the world. Species that have adapted successfully to a barren and inhospitable landscape often occupy a unique niche in this ecosystem, and have little competition for food, water and space. The introduction of new species into ecosystems so simple can have rapid and far-reaching.
The islands face several challenges in the area of conservation and sustainability. Currently over 20% of endemic plant species and 50% of vertebrate species are considered endangered. Moreover, it has come to believe that invasive species pose the greatest threat to native terrestrial biodiversity. Among other challenges, are the excessive harvesting of natural resources of the sea, climate change and pollution. The increasing ease of international travel and the popularity of the Galápagos as a tourist destination means that tourism itself, which before was only as a benefit for the conservation of archpelago, is also part of the problem.
The evolution's way will continue and us with it. Which is our future? a good question to be resolved in future talks. Continue to enjoy the wonders of the Galapagos and if you can travel to the islands before they become extinct.

March 7, 2009

The True Bionic Man

Do you remember the TV series “A man of the 6 million dollars” with Lee Majors, and the saga with the Bionic Woman, and the Bionic Dog (a beautiful german shepherd dog), I remember one chapter in which the bionic man fights with the Saskuatch, two incredible characters. Well, now with the most advance technology the dream comes true!.


This is one of the most amazing invents in technology and medicine. In the past 20 years, biotechnology has become the fastest-growing area of scientific research, with new devices going into clinical trials at a breakneck pace. Now there are available three awasomes miracles of the engineering: the bionic hand, the bionic arm and the bionic eye, remember the eye of Lee Majors in the TV serie with telescopic sight, wau!. All these devices are real and try to imitate to live person with real organs.

The bionic hands was created by a company called Touch Bionics, based in Livingston, Scotland, . They developed a fantastic product of engineering: i-LIMB Hand, an intelligent prosthetic hand with 5 mechanical fingers that you can buy for only $18,000 USD, since 2007. This is a wonderful invent.

Touch Bionics is a leading developer of advanced upper-limb prosthetics (ULP). One of the two products now commercially available from the company, the i-LIMB Hand, is a first-to-market prosthetic device with five individually powered digits. This replacement hand looks and acts like a real human hand and represents a generational advance in bionics and patient care.

The Touch Bionics i-LIMB Hand was developed using leading-edge mechanical engineering techniques and is manufactured using high-strength plastics. The result is a next-generation prosthetic device that is lightweight, robust and highly appealing to both patients and healthcare professionals.
Over 200 people have been benefit with this technology, included ex-soldiers from Irak’s war. But this equipment was made in Scotland in 1963, 50 years ago and it was created to replace limbs in patients with effects of Talidomide, an important teratogenic drug. The real idea is offer a multi articulated hand that simulates a real live hand. This invent won the award of The Royal Academy of Engineering of the UK. The hand has two unique features: 1) Articulated fingers that have a micromotor in each hand that allows to move independently the fingers and; 2) The thumb can rotate 90 degrees like a human thumb.

Even other organizations have developed most advanced hands, the i-LIMB is the first commercial hand available for the patients. This product doesn’t require surgery because is controlled by a unique, highly intuitive control system that uses a traditional two-input myoelectric (muscle signal) to open and close the hand’s life-like fingers. Myoelectric controls utilize the electrical signal generated by the muscles in the remaining portion of the patient’s limb. This signal is picked up by electrodes that sit on the surface of the skin. Existing users of basic myoelectric prosthetic hands are able to quickly adapt to the system and can master the device’s new functionality within minutes.

However, a problem was present, the sense of touch. Todd Kuiken et al., developed a system to establish the sense of touch again in mutilated patient, linked the remains nerves of the stump, where the prosthetic arms are located, with the thoracic nerves. His results was published in the PNAS: Redirection of cutaneous sensation from the hand to the chest skin of human amputees with targeted reinnervation PNAS 2007 104:20061-20066; published online before print November 28, 2007, doi:10.1073/pnas.0706525104.

Now, we have a hand with finger movements and sense of touch.

On the other hand, Rehabilitation Institute of Chicago introduced the first woman to be fitted with its "bionic arm" technology. A patient, who had her left arm amputated at the shoulder after a traffic accident, can now grab a drawer pull with her prosthetic hand by thinking, "grab drawer pull." That a person can successfully control multiple, complex movements of a prosthetic limb with his or her thoughts opens up a world of possibility for amputees The "bionic arm" technology is possible primarily because of two facts of amputation. First, the motor cortex in the brain (the area that controls voluntary muscle movements) is still sending out control signals even if certain voluntary muscles are no longer available for control; and second, when doctors amputate a limb, they don't remove all of the nerves that once carried signals to that limb. So if a person's arm is gone, there are working nerve stubs that end in the shoulder and simply have nowhere to send their information. If those nerve endings can be redirected to a working muscle group, then when a person thinks "grab handle with hand," and the brain sends out the corresponding signals to the nerves that should communicate with the hand, those signals end up at the working muscle group instead of at the dead end of the shoulder.

Rerouting those nerves is not a simple task. Dr. Todd Kuiken of the RIC developed the procedure, which he calls "targeted muscle reinnervation." Surgeons basically dissect the shoulder to access the nerve endings that control the movements of arm joints like the elbow, wrist and hand. Then, without damaging the nerves, they redirect the endings to a working muscle group. In the case of the RIC's "bionic arm," surgeons attach the nerve endings to a set of chest muscles. It takes several months for the nerves to grow into those muscles and become fully integrated. The end result is a redirection of control signals: The motor cortex sends out signals for the arm and hand through nerve passageways as it always did; but instead of those signals ending up at the shoulder, they end up at the chest.

To use those signals to control the bionic arm, the RIC setup places electrodes on the surface of the chest muscles. Each electrode controls one of the six motors that move the prosthetic arm's joints. When a person thinks "open hand," the brain sends the "open hand" signal to the appropriate nerve, now located in the chest. When the nerve ending receives the signal, the chest muscle it's connected to contracts. When the "open hand" chest muscle contracts, the electrode on that muscle detects the activation and tells the motor controlling the bionic hand to open. And since each nerve ending is integrated into a different piece of chest muscle, a person wearing the bionic arm can move all six motors simultaneously, resulting in a pretty natural range of motions for the prosthesis.
Now, we have a hand with finger movements, sense of touch and whole upper limb.

It’s not enough even. A group of scientist of Moorfields Eye Hospital NHS Foundation Trust, one of the world's leading centers for eye health, developed a bionic ete to allow blind people see. It isn’t fantastic, is it?

A training system called BrainPort is letting people with visual and balance disorders bypass their damaged sensory organs and instead send information to their brain through the tongue. Now, a company called Second Sight has received FDA approval to begin U.S. trials of a retinal implant system that gives blind people a limited degree of vision.

The Argus II Retinal Prosthesis System can provide sight, the detection of light, to people who have gone blind from degenerative eye diseases like macular degeneration and retinitis pigmentosa. Ten percent of people over the age of 55 suffer from various stages of macular degeneration. Retinitis pigmentosa is an inherited disease that affects about 1.5 million people around the globe. Both diseases damage the eyes' photoreceptors, the cells at the back of the retina that perceive light patterns and pass them on to the brain in the form of nerve impulses, where the impulse patterns are then interpreted as images. The Argus II system takes the place of these photoreceptors. The second incarnation of Second Sight's retinal prosthesis consists of five main parts: a digital camera that's built into a pair of glasses. It captures images in real time and sends images to a microchip. A video-processing microchip that's built into a handheld unit. It processes images into electrical pulses representing patterns of light and dark and sends the pulses to a radio transmitter in the glass. A radio transmitter that wirelessly transmits pulses to a receiver implanted above the ear or under the eye. A radio receiver that sends pulses to the retinal implant by a hair-thin implanted wire.

Well, almost complete our bionic man with: a hand with finger movements, sense of touch, whole upper limb and a bionic eye!

February 28, 2009

Stem cells: Human Trial for Spinal Cord Injuries

Geron Corporation just got permission from the FDA to start human clinical trials of a new medication based on human embryonic stem cells. This will be the first clinical trial of a stem cell based therapy in humans. The new therapy is designed to treat acute spinal cord injuries, and hopes to restore function to the damaged tissues. Translation, to make people who are currently paralyzed walk again.

Medical researchers are praising adult stem cells and their more committed kin, progenitor cells, for their ability to produce different types of specialized cells. The potential of using these cells to repair or replace damaged tissue holds great promise for cancer therapies and regenerative medicine.
However, the question that must first be answered is what determines the ultimate fate of a stem or progenitor cell? According to an article from the Berkeley Laboratory, a team of researchers led by Mark LaBarge and Mina Bissell, appear to be well on the road to finding out. Working with unique microenvironment microarrays (MEArrays) of their own creation, LaBarge, Bissell, and their collaborators, a cell and molecular biologists in Berkeley Lab's Life Sciences Division, have shown that the ultimate fate of a stem or progenitor cell in a woman's breast – whether the cell develops normally or whether it turns cancerous – may depend upon signals from multiple microenvironments.
Previous studies on how microenvironments affect the development of adult human stem or progenitor cells have been based on the behaviour of these cells in culture (in vitro) where they are exposed to a single molecular agent. However, when these cells are in an actual human being (in vivo) they are surrounded by a multitude of other cells plus a supporting network of fibrous and globular proteins called the extracellular matrix (ECM), as well as many other nearby molecules, all of which may be simultaneously sending them instructional signals.
The GRNOPC1 Clinical Program
Patients eligible for the Phase I trial must have documented evidence of functionally complete spinal cord injury with a neurological level of T3 to T10 spinal segments and agree to have GRNOPC1 injected into the lesion sites between seven and 14 days after injury. Geron has selected up to seven U.S. medical centers as candidates to participate in this study and in planned protocol extensions. The sites will be identified as they come online and are ready to enroll subjects into the study.

Although the primary endpoint of the trial is safety, the protocol includes secondary endpoints to assess efficacy, such as improved neuromuscular control or sensation in the trunk or lower extremities. Once safety in this patient population has been established and the FDA reviews clinical data in conjunction with additional data from ongoing animal studies, Geron plans to seek FDA approval to extend the study to increase the dose of GRNOPC1, enroll subjects with complete cervical injuries and expand the trial to include patients with severe incomplete (ASIA grade B or C) injuries to enable access to the therapy for as broad a population of severe spinal cord-injured patients as is medically appropriate.

February 22, 2009

Genomic Research: the next step!

What are the next step forward?

Discovering the sequence of the human genome was only the first step in understanding how the instructions coded in DNA lead to a functioning human being.

The next stage of genomic research will begin to derive meaningful knowledge from the DNA sequence. Research studies that build on the work of the Human Genome Project are under way worldwide.

The objectives of continued genomic research include the following:
  1. Determine the function of genes and the elements that regulate genes throughout the genome.
  2. Find variations in the DNA sequence among people and determine their significance. The most common type of genetic variation is known as a single nucleotide polymorphism or SNP (pronounced “snip”). These small differences may help predict a person’s risk of particular diseases and response to certain medications.
  3. Discover the 3-dimensional structures of proteins and identify their functions.
  4. Explore how DNA and proteins interact with one another and with the environment to create complex living systems.
  5. Develop and apply genome-based strategies for the early detection, diagnosis, and treatment of disease.
  6. Sequence the genomes of other organisms, such as the rat, cow, and chimpanzee, in order to compare similar genes between species.
  7. Develop new technologies to study genes and DNA on a large scale and store genomic data efficiently.
  8. Continue to explore the ethical, legal, and social issues raised by genomic research.

Stem Cells: the basic 2

Pros and Cons of Embryonic and Adult Stem Cells

There are significant medical and scientific differences between embryonic and adult stem cell research and therapy. Here is a comparison between the two types, including some of the advantages and disadvantages of each.

Embryonic Stem Cell Advantages
1. Flexible, appear to have the potential to make any cell
2. Immortal, one ES cell line can potentially provide an endless supply of cells with defined characteristics
3. Availability, embryos from in vitro fertilization clinics
Embryonic Stem Cell Disadvantages
1. Difficult to differentiate uniformly and homogeneously into a target tissue
2. Immunogenic, ES cells from a random embryo donor are likely to be rejected after transplantation
3. Tumorigenic, capable of forming tumors or promoting tumor formation
4. Destructive, destruction of developing human life
Adult Stem Cell Advantages
1. Flexibility, special adult-type stem cells from bone marrow and from umbilical cord have been isolated recently which appear to be as flexible as the embryonic type
2. Inducibility, already somewhat specialized, inducement may be simpler
3. Not immunogenic, recipients who receive the products of their own stem cells will not experience immune rejection
4. Availability, Relative ease of procurement, some adult stem cells are easy to harvest (skin, muscle, marrow, fat), while others may be more difficult to obtain (brain stem cells). Umbilical and placental stem cells are likely to be readily available
5. Non-tumorigenic, tend not to form tumors
6. No harm done to the donor
Adult Stem Cell Disadvantages
1. Limited quantity, can sometimes be difficult to obtain in large numbers
2. Finite, may not live as long as ES cells in culture
3. Less flexible (with the exception of #1 above), may be more difficult to reprogram to form other tissue types
Adult stem cells are a “natural” solution. They naturally exist in our bodies, and they provide a natural repair mechanism for many tissues of our bodies. They belong in the microenvironment of an adult body, while embryonic stem cells belong in the microenvironment of the early embryo, not in an adult body, where they tend to cause tumors and immune system reactions. Most importantly, adult stem cells have already been successfully used in human therapies for many years. As of this moment, NO therapies in humans have ever been successfully carried out using embryonic stem cells. New therapies using adult type stem cells, on the other hand, are being developed all the time. Here are but a few of the many examples of success stories using adult stem cells.
Cancers: Brain Cancer , Retinoblastoma, Ovarian Cancer , Skin Cancer: Merkel Cell Carcinoma, Testicular Cancer, Tumors abdominal organs Lymphoma, Non-Hodgkin’s lymphoma, Hodgkin’s Disease, Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia, Juvenile Myelomonocytic Leukemia, Chronic Myelomonocytic Leukemia, Angioimmunoblastic Lymphadenopathy , Multiple Myeloma, Myelodysplasia, Breast Cancer, Neuroblastoma, Renal Cell Carcinoma, Sarcoma, Ewing’s Sarcoma, Waldenstrom’s macroglobulinemia, Hemophagocytic lymphohistiocytosis. POEMS syndrome, Myelofibrosis. Auto-Immune Diseases: Diabetes Type I (Juvenile), SLE, Sjogren’s Syndrome, Myasthenia, Autoimmune Thrombocytopenia, Scleromyxedema, Scleroderma, Crohn’s Disease, Behcet’s Disease, Rheumatoid Arthritis, Juvenile Arthritis, Multiple Sclerosis, Idiopatic Polychondritis, Systemic Vasculitis, Alopecia Universalis, Buerger’s Disease. Cardiovascular: Acute Heart Damage, Chronic Coronary Artery Disease. Ocular: Corneal regeneration. Immunodeficiencies: Severe Combined Immunodeficiency Syndrome SCID, X-linked Lymphoproliferative Syndrome, X-linked Hyper-immunoglobulin M Syndrome. Neural Degenerative Diseases and Injuries: Parkinson’s Disease, Spinal Cord Injury, Stroke Damage. Anemias and Other Blood Conditions: Sickle Cell Anemia, Sideroblastic Anemia, Aplastic Anemia, Red Cell Aplasia, Amegakaryocytic Thrombocytopenia, Thalassemia, Primary Amyloidosis, Diamond Blackfan Anemia, Fanconi’s Anemia, Chronic Epstein-Barr Infection. Wounds and Injuries: Limb Gangrene, Surface Wound Healing, Jawbone Replacement, Skull Bone Repair. Other Metabolic Disorders: Hurler’s Syndrome, Osteogenesis Imperfecta, Krabbe’s Leukodystrophy, Osteopetrosis, Cerebral X-Linked Adrenoleukodystrophy. Liver Disease: Chronic Liver Failure, Liver Cirrhosis. Bladder Disease: End-Stage Bladder Disease.