SIGMAR1 Gene Mutation Linked To Juvenile ALS Development, Researchers Identify

From the Kingdom of Saudi Arabia, investigators have identified a mutation on the SIGMAR1 gene linked with the development of juvenile amyotrophic lateral sclerosis (ALS). Sigma-1 receptors, which are involved in motor neuron function and disease development, are affected by the gene variant, according to a study published in the Annals of Neurology, a journal of the American Neurological Association and the Child Neurology Society.

ALS, (Lou Gehrig's disease), is a progressive neurodegenerative disorder attacking brain and spinal cord nerve cells (neurons) which are responsible for controlling voluntary muscle movement. The degeneration of upper and lower motor neurons slowly weakens the muscles they control, which will ultimately lead to paralysis and death from respiratory failure.

The study revealed that yearly 1 to 3 per 100,000 individuals are affected by ALS, of which 90% of cases have no family history of the disease (sporadic ALS) with the remaining 10% of cases showing more than one family member being affected by it (familial ALS). Characterized by age of onset below 25 years, juvenile ALS is a rare and sporadic disorder which makes it hard to establish incidence rates. Having being diagnosed at 21, physicist, Professor Stephen Hawking is one of the most well known juvenile ALS patients.

Earlier investigations discovered that mutation of the superoxide dismutase 1 (SOD1) gene accounts for 20% of familial and 5% of sporadic ALS cases, while ALS2 and SETX gene mutations have been reported in juvenile ALS cases.

Dr. Amr Al-Saif from the King Faisal Specialist Hospital and Research Center in Riyadh, KSA, who is leading the present investigation, performed genetic testing on four patients from an ALS family who were diagnosed with juvenile ALS to study mutations suspected in disease development.

Using direct sequencing to detect the genetic variants, together with gene mapping on the DNA of study participants, researchers identified a shared homozygosity region in the affected individuals, and gene sequencing of SIGMAR1 showed a mutation affecting the encoded protein, Sigma-1 receptor. Cells with the mutant protein were not as resistant to programmed cell death (apoptosis) induced by stress to the endoplasmic reticulum.

What is Hemophilia, What is Haemophilia

Hemophilia is a group of inherited blood disorders in which the blood does not clot properly. Hemophilia is the standard international spelling, also known as haemophilia in the UK, other translations include: hémophilie, hemofilie, hemofili, hemofilia, hämophilie, emofilia. We will use the standard international spelling for the purpose of this section.
Bleeding disorders are due to defects in the blood vessels, the coagulation mechanism, or the blood platelets. An affected individual may bleed spontaneously or for longer than a healthy person after injury or surgery.
The blood coagulation mechanism is a process which transforms the blood from a liquid into a solid, and involves several different clotting factors. The mechanism generates fibrin when it is activated, which together with the platelet plug, stops the bleeding.
When coagulation factors are missing or deficient the blood does not clot properly and bleeding continues.
Patients with Hemophilia A or B have a genetic defect which results in a deficiency in one of the blood clotting factors.
Queen Victoria was a carrier and passed the mutation to her son Leopold, and through several of her daughters to members of the royal families of Spain, Russia, and Germany.
Tsarevich Alexei Nikolaevich, son of Nicholas II (Russia) suffered from hemophilia and was a descendant of Queen Victoria - Rasputin was successful in treating his hemophilia, it was claimed.

tuberculosis

Using the Baculillus Calmette-Guerin (BCG) - the germ commonly used to inoculate against tuberculosis (TB), researchers have found a potential new mechanism to stimulate the body's own ability to fight cancer. The discoveries are published online this week in the British Journal of Cancer.

The investigators, Dr Wai Liu and Professor Angus Dalgleish from St George's, University of London, say this new information suggests a mechanism by which vaccines may increase the anti-cancer activity of therapies which are available at present. Although, they warn that this investigation is in its primary stages and a lot more research is needed before patients will benefit.

Human tumor cells outside of the body were conducted in laboratory-based experiments; they showed that a small amount of BCG can instruct white blood cells to create chemicals called cytokines, raising the chances of tumor cells being detected by the body's immune system.

Phase 2 Trial Of Lexicon's LX1032, Telotristat Etiprate, Shows Positive Results In Carcinoid Syndrome

Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, announced positive, top-line proof-of-concept data from its recently completed Phase 2 study in carcinoid syndrome with LX1032, telotristat etiprate. Carcinoid syndrome is a chronic condition caused by neuroendocrine tumors that usually originate from the gastrointestinal tract. It is characterized by severe diarrhea and flushing episodes with long-term consequences including malnutrition, heart disease, and death. Symptoms of carcinoid syndrome have been linked to excess production of serotonin by metastatic tumor cells. Telotristat etiprate is designed to reduce serotonin production.

"Telotristat etiprate is our third drug candidate to demonstrate proof of concept in patients in Phase 2," said Dr. Arthur T. Sands, Lexicon's president and CEO. "Based on the positive results of this U.S. study, as well as encouraging observations from our clinical trial in Europe, we intend to discuss a Phase 3 development plan for carcinoid syndrome with the FDA."

The randomized, double-blind, placebo-controlled study was conducted in the United States in 23 patients with carcinoid syndrome who were refractory to currently available therapy. Patients in the study had metastatic carcinoid disease and were experiencing an average of about six bowel movements per day at baseline. Patients received either placebo (n=5) or one of four doses of telotristat etiprate (n=18) daily for 28 days. The primary endpoint of the study was safety and tolerability. Efficacy measures included change in bowel movement frequency, relief of symptoms, and reduction in serotonin synthesis.

Telotristat etiprate was well tolerated, and adverse events in the study were usually mild to moderate with similar frequencies overall between treatment groups and placebo. Five telotristat etiprate patients achieved clinical responses characterized by reductions of at least 30% in the number of bowel movements per day for two weeks or more during the study. Six telotristat etiprate patients reported adequate relief of carcinoid symptoms at the end of the study. There were nine telotristat etiprate patients with a complete biochemical response defined as a reduction of at least 50% in urinary 5-HIAA, a biomarker of serotonin synthesis. No patients on placebo experienced a clinical response, adequate relief of symptoms, or biochemical response during the study. The difference between telotristat etiprate and placebo in bowel movement frequency ranged between 1.6 and 2.9 bowel movements/day across telotristat etiprate doses, all favoring telotristat etiprate treatment. Also of note, all eligible patients elected to continue treatment with telotristat etiprate under an extension protocol.

Preliminary data were also reported from a separate, ongoing, open-label, single-arm study of telotristat etiprate in Europe. To date, 5 out of 6 patients with refractory carcinoid syndrome have experienced sustained reductions of at least 30% in bowel movement frequency when treated with telotristat etiprate. Two of these responses were within the first 4 weeks of therapy, while three more occurred between 4 and 8 weeks of treatment under the 12-week protocol.

"The Phase 2 data clearly show a reduction in bowel movements and symptom relief in a population that has exhausted all standard-of-care treatment options," said Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon. "The Phase 2 data are also consistent with preliminary results from the European study, where there appear to be some early responses and additional benefit with continued treatment. We look forward to presenting detailed results at a scientific meeting later this year."

Source: Lexicon Pharmaceuticals, Inc

alergy

Prenatal pet exposure, a mother's delivery mode and race are influential factors in a child's risk of developing allergies by age 2, according to a Henry Ford Hospital study.

In a study believed to be the first of its kind, Henry Ford researchers found that babies who have indoor prenatal pet exposure have a pattern of lower levels of the antibody Immunoglobulin E, or IgE, between birth and age 2. IgE is linked to the development of allergies and asthma.

Key findings:

    IgE levels were 28 percent lower during infancy in babies who had indoor prenatal pet exposure compared to babies from pet-free homes.
    IgE levels were 16 percent lower in infants who had indoor prenatal pet exposure and were born vaginally compared to 43 percent in infants who had indoor prenatal pet exposure and were born by cesarean section.
    IgE levels were 33 percent lower in infants who had indoor prenatal pet exposure and were either European, Asian or Middle Eastern descent compared to compared to
    10 percent lower in infants who had indoor prenatal pet exposure and were African-American.

The findings are published online at The Journal of Allergy and Clinical Immunology at http://www.jacionline.org/inpress

"We believe having a broad, diverse exposure to a wide array of microbacteria at home and during the birthing process influences the development of a child's immune system" says Christine Cole Johnson, Ph.D., MPH, chair of Henry Ford's Department of Public Health Sciences and senior author of the study.

Dr. Johnson says the findings support the so-called hygiene hypothesis, which theorizes that early childhood exposure to infectious agents affects the immune system's development and onset of allergies and asthma.

Prior published research by Henry Ford's Department of Public Health Sciences has shown that pet exposure has a protective effect against early allergy development. She theorizes that babies born through the birth canal are exposed to a higher and more diverse burden of bacteria, further boosting the immune system's protection against allergies.

"Our findings may provide insight into the biological mechanisms that increase the risk for allergic disorders," Dr. Johnson says. She theorizes that "genetic variants" may explain the higher levels of IgE levels in African American newborns.

Henry Ford researchers followed 1,187 newborns August 2003 and November 2007 and collected blood samples for measuring IgE levels at birth, six months, one year and two years.

Of the birth mothers, 62 percent were African American and 33 percent were European Americans. Of the babies born, 751 were delivered vaginally and 436 were delivered cesarean. There was at least one indoor pet in the homes of 420 mothers.

The study was funded by the National Institute of Allergy and Infectious Diseases.

healthy recipes

People are seeking more healthful diets for weight loss, disease prevention and general well being. Counting carbohydrates, limiting fats and modifying portions are all popular approaches to weight loss. People who find the right balance between a varied nutritious diet and physical activity enjoy a stable weight and overall health.
Luckily, turkey adapts to all meals plans. It's a delicious, versatile protein. A 3-ounce serving of boneless, skinless turkey breast contains 26 grams of protein, 1 gram of fat and 0 grams of saturated fat. That's 8 percent more protein than the same size serving of boneless skinless chicken breast or trimmed top loin beefsteak.

health and safety at work act

health and safety at work act about Health and Safety at Work etc Act 1974

The Health and Safety at Work etc Act 1974 , also referred to as HASAW or HSW, is the primary piece of legislation covering occupational health and safety in the United Kingdom. The Health and Safety Executive is responsible for enforcing the Act and a number of other Acts and Statutory Instruments relevant to the working environment.
The full text of the Act is available at the UK legislation website link to external website, where it can also be downloaded free of charge.

    Health and Safety at Work etc Act 1974 link to external website This is current at September 2006. Please see the Disclaimer.

Statutory instruments are the secondary types of legislation made under specific Acts of Parliament. These cover a wide range of subjects, from control of asbestos at work, diving, escape and rescue from mines, ionising radiation and working at height.

See Legislation enforced by HSE for more details.

If you need further advice on legal matters concerning the workplace, please contact HSE Infoline or consult Sources of information and external advisory services.
Disclaimer

The information on this site is regularly updated and checked for accuracy and completeness. However it is important to note that legal information must be used with a degree of caution.

Users must be aware that whilst an Act or Statutory Instrument (SI) may still be in force, parts may have been superseded by later legislation or completely withdrawn. If you use a printed or online version of an Act or Statutory Instrument this will generally be in the form that it was originally produced.

Any withdrawn or amended sections will still be contained within the Act or SI and there will be nothing in the document to identify those sections that no longer apply.

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