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An Increase in Leptin Could Promote Colorectal Cancer

While researchers have known that obesity increases the risk for the development of colon cancer, the underlying molecular mechanisms have remained unclear.
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Now, for the first time, researchers have found that an increase in leptin, a cytokine that is normally increased in obese or overweight individuals, may promote colorectal neoplasms by activating colorectal cancer stem cells.

Cancer stem cells constitute a small subfraction of tumor cells that are characterized by long lifespan and capacity for self-renewal, and are responsible for tumor development, resistance to treatments and cancer recurrence. In colon cancer, leptin is able to increase the growth, survival, and resistance to certain chemotherapy treatments in this key cell population.

Leptin, a fat tissue-derived pluripotent cytokine regulating appetite and energy balance in the brain, also controls many physiological and pathological processes in peripheral organs, including carcinogenesis.

Colon cancer has increased in developed countries, possibly due to sedentary lifestyles and high caloric diets. Prior research has linked obesity to colorectal cancer risk by .4-1.0 fold in men and up to 2.0 fold in premenopausal women.

“Since targeting cancer stem cells may be a translationally relevant strategy to improve clinical outcomes, interfering with leptin signaling by targeting leptin receptors might become a novel attractive option for colorectal cancer treatment, particularly in obese patients,” says senior author of the study, Eva Surmacz.

“It is important to consider that cancer stem cells have been identified in several human malignancies,” says Monica Bartucci, study co-author. “Understanding how cancer stem cells interact with a tumor environment, including hormones like leptin, is likely to have significant implications for treatment management of different cancer types in human patients. We hope, in collaboration with Dr. Surmacz, not only to test the effects of leptin antagonist compounds on colon cancer stem cells but also to study the results of leptin stimulation on cancer stem cells isolated in other cancer tissues.”

Source: Elements4Health

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Banking on Stem Cells

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Advertisements in the media advise parents to “plan and protect your children’s future and their health status”. These are not commercials for insurance plans, but private stem cell banking facilities, where, for a steep price, your baby’s umbilical cord stem cells can be preserved for future use.
..click & see

Stem cells are in the news. Independent national and international laboratories are making claims and counterclaims about the “miracles” they have achieved with them. Paralysed people have been able to walk, rare degenerative nervous and muscular system diseases been reversed, and some cancers of the blood cells cured. People with terminal illnesses have also been offered hope…..click & see

Actress Lisa Ray underwent stem cell therapy for multiple myeloma, a cancer of the white blood cells...click & see

Stem cells may be embryonic, adult or derived from umbilical cords. Embryonic stem cells are obtained from the extra fertilised eggs at in vitro fertilisation (IVF) centres. The use of these cells is controversial, as, theoretically, they have the potential to become human beings. They are the “spare babies” belonging to a particular IVF couple. When supplied to a stem cell research facility, they are grown in a nutrient broth in a culture dish and used for research or treatment.

Adult stem cells are found in bone marrow. These are harvested from the bone marrow of living donors. It’s a surgical procedure done under anaesthesia with some post-operative discomfort. The cells are capable of eventually forming either various types of blood cells or stromal cells from which cartilage and fat tissues arise.

Haematologists treat a variety of hereditary blood disorders and some of the blood cancers with either autologous (the person’s own) stem cells or compatible donor cells from bone marrow transplants. This technology has been used for the last 30 years. Bone marrow transplants are life saving for people with certain blood cancers. They can also be used for serious blood disorders such as aplastic anaemia. They can also help boost the immune system if it is impaired because of an inherited genetic defect or destroyed by cancer.

Umbilical cords are a rich and non-controversial source of stem cells. Cord blood has a greater ability to generate new blood cells than does bone marrow. Also, smaller quantities of cord blood cells are needed for successful transplantation. These cords are normally discarded along with the placenta from labour wards all over the world.

At present, in India, patients who require stem cell treatment or a bone marrow transplant have to search for a relative who is an appropriate tissue match. Sometimes even close first-degree relatives like a parent or sibling are not compatible. India does not as yet have a centralised national bone marrow registry to match recipients and donors.

Some foresighted countries with efficient national health schemes like the United Kingdom and Brazil do have public cord blood banks. Blood is screened for infective agents, documented in a registry and stored. The chances of finding compatible stem cells are high because of the large volumes stored.

India has private cord blood banks which store blood only for the use of that particular child for a period of 21 years. It may be a cost effective option for parents who have a family history of certain genetic diseases, such as severe hereditary anaemias, immune disorders or certain cancers. Even then, the chance that the blood can be used for that particular child is only 1 in 2,000. In families with no such risk factors, there is only about a 1-in-20,000 chance of the child ever needing a stem cell transplantation. Also, even if the child does require a stem cell transplant, it is unlikely that his or her own cord blood would be the desired source of stem cells. The same chromosomal or genetic defect causing the leukaemia, any other cancer or metabolic disorder, is likely to be present in the child’s stem cell line. There is no proof that a transplant using the child’s own stem cells is effective or even safe, especially in cases of childhood cancers.

Indians have a very diverse genetic make-up. The large-scale collection and storage of cord blood in public banks will be very useful. It can be used for matched unrelated recipients who urgently need blood cell transplants.

Stem cells are probably the future of medicine and the human race. They are multifaceted and have the potential to develop into different cell types. They can theoretically keep dividing as long as the person is alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another specialised cell like a muscle cell, red blood cell, or brain cell. This means stem cells can be infused as a sort of emergency repair mechanism to replenish damaged tissues.

Perhaps disease, aging, cancer and even death can be controlled and conquered. And living healthily forever may become a reality.

Source
:The Telegraph (Kolkata, India)

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Ailmemts & Remedies Pediatric

Bubble Boy Disease

Other Names: Severe combined immunodeficiency (SCID), or Boy in the Bubble Syndrome, (also known as “Alymphocytosis,” “Glanzmann–Riniker syndrome,” “Severe mixed immunodeficiency syndrome,” and “Thymic alymphoplasia”


Definition:

It is a genetic disorder in which both “arms” (B cells and T cells) of the adaptive immune system are crippled, due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency. It is also known as the “bubble boy” disease because its victims are extremely vulnerable to infectious diseases and some of them, such as David Vetter, become famous for living in a sterile environment.

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David Vetter poses inside of his bubble in his Houston home in this Dec. 17, 1976

The body’s immune system fights against diseases and infections. The SCID syndromes are inherited disorders that result in severe defects in the immune system. White blood cells (which fight infection) are produced in the bone marrow by stem cells. In people with SCID, the bone marrow stem cells are absent or defective. This leaves the affected person open to any and all germs around him because he has no way to fight them off.

Prevalence:-
The most commonly quoted figure for the prevalence of SCID is around 1 in 100,000 births, although this is regarded by some to be an underestimate of the true prevalence; and a figure of about 1 in 65,000 live births has been reported for Australia.

Recent studies indicate that one in every 2,500 children in the Navajo population inherit severe combined immunodeficiency. This condition is a significant cause of illness and death among Navajo children. Ongoing research reveals a similar genetic pattern among the related Apache people.

Types
:-
1. X-linked severe combined immunodeficiency:

Most cases of SCID are due to mutations in the gene encoding the common gamma chain (?c), a protein that is shared by the receptors for interleukins IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. These interleukins and their receptors are involved in the development and differentiation of T and B cells. Because the common gamma chain is shared by many interleukin receptors, mutations that result in a non-functional common gamma chain cause widespread defects in interleukin signalling. The result is a near complete failure of the immune system to develop and function, with low or absent T cells and NK cells and non-functional B cells.
The common gamma chain is encoded by the gene IL-2 receptor gamma, or IL-2R?, which is located on the X-chromosome. Therefore, immunodeficiency caused by mutations in IL-2R? is known as X-linked severe combined immunodeficiency. The condition is inherited in an X-linked recessive pattern.


2.Adenosine deaminase deficiency:-

The second most common form of SCID after X-SCID is caused by a defective enzyme, adenosine deaminase (ADA), necessary for the breakdown of purines. Lack of ADA causes accumulation of dATP. This metabolite will inhibit the activity of ribonucleotide reductase, the enzyme that reduces ribonucleotides to generate deoxyribonucleotides. The effectiveness of the immune system depends upon lymphocyte proliferation and hence dNTP synthesis. Without functional ribonucleotide reductase, lymphocyte proliferation is inhibited and the immune system is compromised.

3. Omenn syndrome:

The manufacture of immunoglobulins requires recombinase enzymes derived from the recombination activating genes RAG-1 and RAG-2. These enzymes are involved in the first stage of V(D)J recombination, the process by which segments of a B cell or T cell’s DNA are rearranged to create a new T cell receptor or B cell receptor (and, in the B cell’s case, the template for antibodies).Certain mutations of the RAG-1 or RAG-2 genes prevent V(D)J recombination, causing SCID.

4.Bare lymphocyte syndrome:-

MHC class II is not expressed on the cell surface of all antigen presenting cells. Autosomal recessive. The MHC-II gene regulatory proteins are what is altered, not the MHC-II protein itself.

5.JAK3 :-  Janus kinase-3 (JAK3) is an enzyme that mediates transduction downstream of the ?c signal. Mutation of its gene also causes SCID.

6.Artemis/DCLRE1C:-
Mortan Cowan, MD, director of the Pediatric Bone Marrow Transplant Program at the University of California-San Francisco, noted that although researchers have identified about a dozen genes that cause SCID, the Navajo and Apache population has the most severe form of the disorder. This is due to the lack of a gene designated Artemis. Without the gene, children’s bodies are unable to repair DNA or develop disease-fighting cells.


Symptoms:

Chronic diarrhea, ear infections, recurrent Pneumocystis jirovecii pneumonia, and profuse oral candidiasis commonly occur. These babies, if untreated, usually die within 1 year due to severe, recurrent infections. However, treatment options are much improved since David Vetter.


You may click to see :

The list of signs and symptoms mentioned in various sources for SCID includes the 35 symptoms listed below:

Causes
:
Click to see :New Genetic Cause Of Boy In The Bubble Syndrome :

New gene mutation found to cause ‘bubble boy disease’ :


How Gene Defects Cause Disease :


Diagnosis:

Several US states are performing pilot studies to diagnose SCID in newborns through the use of T-cell recombinant excision circles.[citation needed] Wisconsin and Massachusetts (as of February 1, 2009) screen newborns for SCID.

Despite these pilot programs, standard testing for SCID is not currently available in newborns due to the diversity of the genetic defect. Some SCID can be detected by sequencing fetal DNA if a known history of the disease exists. Otherwise, SCID is not diagnosed until about six months of age, usually indicated by recurrent infections. The delay in detection is because newborns carry their mother’s antibodies for the first few weeks of life and SCID babies look normal.

You may click to see :Diagnostic Tests for SCID :

Treatment
:-
The most common treatment for SCID is bone marrow transplantation, which has been successful using either a matched related or unrelated donor, or a half-matched donor, who would be either parent. The half-matched type of transplant is called haploidentical and was perfected by Memorial Sloan Kettering Cancer Center in New York and also Duke University Medical Center which currently does the highest number of these transplants of any center in the world. David Vetter, the original “bubble boy”, had one of the first transplantations but eventually died because of an unscreened virus, Epstein-Barr (tests were not available at the time), in his newly transplanted bone marrow from his sister. Today, transplants done in the first three months of life have a high success rate. Physicians have also had some success with in utero transplants done before the child is born and also by using cord blood which is rich in stem cells.

More recently gene therapy has been attempted as an alternative to the bone marrow transplant. Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID. In 1990, 12-year-old Ashanthi DeSilva became the first patient to undergo successful gene therapy. Researchers collected samples of Ashanthi’s blood, isolated some of her white blood peripheral T cells, and incorporated into them a virus engineered to contain a healthy immune system enzyme: adenosine deaminase (ADA) gene. These cells were then injected back into her body. She is now given a weekly shot of ADA that without would have her destined for a life of isolation. In 2000, the first gene therapy “success” resulted in SCID patients with a functional immune system. These trials were stopped when it was discovered that two of ten patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. In 2007, four of the ten patients have developed leukemias [11]. Work is now focusing on correcting the gene without triggering an oncogene. No leukemia cases have yet been seen in trials of ADA-SCID, which does not involve the gamma c gene that may be oncogenic when expressed by a retrovirus.

Trial treatments of SCID have been gene therapy’s only success; since 1999, gene therapy has restored the immune systems of at least 17 children with two forms (ADA-SCID and X-SCID) of the disorder.

You may click to see :
Drugs and Medications used to treat SCID:
A new hope for gene therapy

Breakthrough for “Bubble Boy” Disease

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:

http://en.wikipedia.org/wiki/Severe_combined_immunodeficiency#cite_note-Bolognia-0
http://rarediseases.about.com/od/immunedisorders/a/scid.htm
http://www.wrongdiagnosis.com/s/scid/intro.htm

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Your Gums May Save Your Life

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Stem cells now have an easy and superior source — gum tissue.As per latest lab report.

……………....CLICK  & SEE

The history of modern medicine has rarely witnessed anything as controversial as stem cell therapy. Exponents swear by its potential to change the face of treatment and alleviate suffering. Taking advantage of this, unscrupulous medicos across the world have used the therapy to make a quick buck. Their claims — which are, of course, unsubstantiated — have caused further damage, almost discrediting this treatment method that explores the possibility of introducing new cells into damaged tissues to cure a disease or an injury.

As the name suggests, stem cells are capable of growing into various types of cells found in the human body. They can help form bones, muscles and even heart and brain cells. Medical scientists hope they can offer an answer to many diseases that have been so far regarded as incurable.

An enormous amount of research is required to take the therapy to a standard where it can be put to use extensively. However, there is a problem — providing more and more researchers easy access to stem cells is a daunting task.

A team of Indian researchers has found a better source for at least one important type of stem cells. Scientists led by Mohan Wani at the National Centre for Cell Science (NCCS), Pune, have shown that mesenchymal stem cells (MSCs) — which have the potential to regenerate muscles, bones and even nerve cells — can be extracted from human gum tissue.

Stem cells are of different types. Some are pluripotent — that is, they can be grown into all types of cells found in the human body. Human embryos are a good source of pluripotent stem cells. Most of the ethical issues relating to stem cell research are in connection with these stem cells.

The MSCs, on the other hand, are multipotent — that is, they can grow into only certain types of cells. Scientists have shown in the lab that MSCs can be used to regenerate bones, cartilage and muscles, but this is yet to become a line of treatment.

Studies in the past have shown that MSCs are present in virtually all organs and tissues in the body. But they are normally harvested from bone marrow, the soft tissue inside the bones. One of the reasons, perhaps, is that the technique to extract bone marrow has been around for more than three decades. Bone marrow transplant has been a popular method of treating many blood disorders, including thalassaemia and certain blood cancers.

However, the process of extracting bone marrow cells is painful, particularly for the elderly. “Harvesting bone marrow from the iliac crest of the pelvic bone is a painful course. Moreover, you need to extract the tissue in a large quantity as the number of MSCs in it is low,” says Wani.

Gum tissue, on the other hand, not only contains more stem cells but also of a more homogenous type. Bone marrow contains more than one type of stem cell. Besides, the process of harvesting stem cells from gum tissue is easy and leaves no scar, says Wani.
…………………….
The NCCS work, which appeared in the latest issue of the journal Biochemical and Biophysical Research Communications , says that gum tissue can be a superior source of stem cells for several reasons. The yield of MSCs from bone marrow ranges from 0.001 to 0.01 per cent. In case of gum tissue, “we are expecting a four to six-fold increase,” says Wani.

The study looks interesting, says Maneesha Inamdar, a researcher at the Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, who works in the area of stem cells. Oral cells are more accessible and hence could be a better alternative to bone marrow, she observes.

Another expert from Christian Medical College, Vellore, however, is not so hopeful. “I do not anticipate people lining up to have their gingival (gum) tissue biopsied to produce these cells, nor do I see any dramatic impact of the use these cells in the clinic in the near future,” says the scientist, who prefers to remain anonymous.

There are other benefits of stem cells extracted from gum tissue, says Wani. The scientists, who grew many generations of the cells in the lab, found that they could hold their inherent properties for much longer than those derived from bone marrow. “These cells exhibited no abnormalities and are hence safe for clinical applications,” Wani told KnowHow.

As the next step, the Pune researchers plan to use to the stem cells derived from gum tissue to regenerate different types of human tissues.

So take care of your gums, for they will take care of you one day, if needed.

Massaging of Gum with a finger and rinsing the mouth at least two to three times daily after  eating, is the easiest way to keep the gum muscles strong &  healthy.

You may click to see:->Home Treatments for Gum Disease

Source : The Telegraph (Kolkata,India)

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Keep Firm Muscle Tone with the Age

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Scientists have found and manipulated body chemistry linked to the aging of muscles, and were able to restore the ability of old human muscle to repair and rebuild itself.
click & see
Importantly, the research also found evidence that aging muscles need to be kept in shape, because long periods of atrophy are more challenging to overcome. Older muscles do not respond as well to sudden bouts of exercise. And rather than building muscle, older people can instead generate scar tissue if they exercise after long periods of inactivity.

Previous studies have shown that adult muscle stem cells have a receptor called Notch, which triggers growth when activated. An enzyme called mitogen-activated protein kinase (MAPK) regulates Notch activity.

In the lab, the researchers cultured old human muscle and forced the activation of MAPK. The regenerative ability of the old muscle was significantly enhanced.

Resources:
Live Science September 30, 2009
EMBO Molecular Medicine September 30, 2009 [Epub ahead of Print]