Members & Followers

Friday, July 31, 2015

7 Strategies to Developing a Positive Mental Attitude

7 Strategies to Developing a Positive Mental Attitude

One of the best ways to increase your chance of success in all areas of life is to develop a positive mental attitude.
Taking a positive attitude toward life makes you a happier person all round, and one that other people in your life look up to, and want to spend time with.
There’s even evidence that having a positive attitude can help lower stress levels and improve your health.
Maintaining a Positive Mental Attitude
Here are 7 ways that we can all work toward developing a positive outlook on life.
1. Focus On the Present
Mark Twain said,
I’ve been through terrible things in my life, some of which actually happened.
He was pointing out the fact that we often add to our problems by building them up in our minds to be bigger than they really are.
How often do you find that things you worry about for days end up not happening at all, or not being as big a problem as you thought?
But, by focusing on the present as much as possible, you can minimize the worries and fears that lead to negative emotions.
2. Use Positive Language
Do you ever notice how much of what you say is negative?
Some people constantly complain about the weather, their work, their spouse, their neighbors, and any number of other things.
We all do it from time to time.
However, it’s good to remind ourselves that our words are shaped by our thoughts, and the more we can look for positive things to say, the more positive our thoughts will become. Willie Nelson said it well when he said,
Once you replace negative thoughts with positive ones, you’ll start having positive results.
Make it your endeavor to commit to positive thinking. So, each day when you wake up give yourself a mini pep talk – what do you want to achieve? How will you react to trying situations? How will you avoid negative thoughts? Remember, thinking positive is a habit, which means it’s possible to learn how to do it.
3. Accept When Things Aren’t Perfect
It can be difficult to let go of the need for perfection and control in your life, but sometimes it’s very liberating to simply accept that things will not always go the way you hoped, and that’s okay.
Sometimes things happen that are out of your control, and rather than wasting your energy on negative emotions, it’s better to just accept that things didn’t go the way you planned or wanted.
Remember, most things pass with time.
4. Mix With Positive People 
It’s a fact of human nature that we tend to mimic the people we spend the most time with.
Think of how teenagers tend to conform to the social code of their friends. It’s the same for everyone else, too.
So, the more frequently you spend time with positive thinking people, the more likely it is that you will begin to think and act in a similar fashion.
Also, don’t underestimate the power of laughing either, it has a wonderful way of reducing stress, connecting you with those around you, and generally making you feel better all round. I wholeheartedly agree with William James when he said,
We don’t laugh because we’re happy, we’re happy because we laugh.
5. Contribute in A Meaningful Way
one of the best ways to feel more positive is to contribute to your community in some way.
It can be tremendously uplifting to help others, whether it’s through the use of your time, skills or financial contributions.
As well as the good feelings that come with making a difference in someone’s life, contributing your time and effort to a cause, allows you a brief escape from your current problems, and perhaps may even allow you see your troubles in a different light.
6. Keep Learning 
Develop a curiosity about the world around you, and the people in it. No matter what situation you’re in right now, there is always something we can learn from it.
Taking a real interest in life gives you energy, it helps create new ideas in your mind, and gives you a different way of thinking about things, that can have a positive impact on your life as a whole.
7. Be Grateful
Spend a little time each day thinking of things that you are truly thankful for in your life.
Reminding yourself of all the reasons you have to be grateful, helps to maintain some focus on your situation.
Being thankful will often turn initial anger or frustration into something more positive. Remember, we all have weaknesses, but focusing on your strengths prevents them getting the better of us.
A good practice to get into is that of keeping a gratitude journal. This is where you make a note of at least 5 things that make you happy or thankful each day. This is one of the best ways to foster the habit of gratitude.

Finally, keep in mind that how you view your life is your choice. No one is forcing you to have a negative attitude, so take control and change it for a happier, more energetic, and more enthusiastic life.

       "Remember....Research is the key to your cure!"

Wednesday, July 29, 2015

Alnylam and Collaborators Publish Pre-Clinical Results with ALN-AS1, an RNAi Therapeutic Targeting Aminolevulinic Acid Synthase-1 (ALAS-1) for the Treatment of Hepatic Porphyrias, in the Proceedings of the National Academy of Sciences

We need research volunteers, if you have an Acute Porphyria and would like more information on this and other studies please contact Natalia APF 1-866-APF-3635

Alnylam and Collaborators Publish Pre-Clinical Results with ALN-AS1, an RNAi Therapeutic Targeting Aminolevulinic Acid Synthase-1 (ALAS-1) for the Treatment of Hepatic Porphyrias, in the Proceedings of the National Academy of Sciences

05.21.2014

- New Paper Documents Previously Presented Proof-of-Concept Results in Mouse Model of Acute Intermittent Porphyria (AIP) -
- RNAi Therapeutics Targeting ALAS-1 Completely Block Production of Toxic Heme Biosynthesis Intermediates that Cause Symptoms and Disease Pathology -
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the publication in the Proceedings of the National Academy of Sciences (PNAS) of pre-clinical results with RNAi therapeutics targeting aminolevulinic acid synthase-1 (ALAS-1) for the treatment of hepatic porphyrias, including acute intermittent porphyria (AIP). In the paper, titled "RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice," Alnylam scientists and collaborators at the Icahn School of Medicine at Mount Sinai in New York City documented results from pre-clinical models of the human disease showing that RNAi therapeutics targeting ALAS-1 can completely block the abnormal production of toxic intermediates of the heme biosynthesis pathway that cause the symptoms and disease pathology of AIP. This new paper provides proof of concept for an RNAi therapeutic for the treatment of AIP.
"Our data in a mouse model of AIP, now published in PNAS, demonstrate that RNAi therapeutics targeting ALAS-1 can achieve potent, rapid, and durable suppression of the toxic heme biosynthesis intermediates that cause the symptoms and disease pathology of AIP. As such, these findings provide key pre-clinical proof-of-concept data for our ALN-AS1 program. We believe ALN-AS1 has the potential to be a transformative therapy for patients with hepatic porphyrias including AIP, an ultra-rare genetic disease with enormous unmet medical need," said Rachel Meyers, Ph.D., Vice President, Research and RNAi Lead Development of Alnylam. "We are currently advancing our Development Candidate for ALN-AS1, which employs our Enhanced Stabilization Chemistry-GalNAc-conjugate technology. This technology enables subcutaneous dosing with improved potency and durability, and a wide therapeutic index, and is now clinically validated based on results from our hemophilia program. We are on track to file an Investigational New Drug application for ALN-AS1 in late 2014 or early 2015, and look forward to advancing this investigational medicine to patients."
The acute hepatic porphyrias, including AIP, are ultra-rare orphan diseases caused by loss-of-function mutations in enzymes involved in heme biosynthesis, leading to accumulation of toxic heme intermediate precursors. In the case of AIP, there are approximately 5,000 patients in the U.S. and Europe that suffer acute, life-threatening porphyria attacks every year; there are approximately 500 patients afflicted with recurrent debilitating attacks, often occurring once per month. Treatment options for AIP patients suffering from an attack are limited, and include the use of heme preparations that show limited efficacy and are associated with a number of complications including phlebitis, iron overload, and infections related to the need for central venous access in some patients. Currently, there are no approved drugs available to prevent attacks from occurring. Alnylam's approach is to knock down ALAS-1, an enzyme upstream of porphobilinogen deaminase (PBGD), the defective gene in AIP. RNAi-mediated silencing of hepatocyte ALAS-1 could reduce the abnormal production of the toxic heme intermediates, specifically aminolevulinic acid (ALA) and porphobilinogen (PBG), which mediate the symptoms and disease pathology in AIP patients as well as in some of the other acute hepatic porphyrias. Alnylam believes that a subcutaneously administered RNAi therapeutic targeting ALAS-1 has the potential to be used as a prophylactic approach to prevent attacks, and also as a therapy for acute attacks.
In the new paper published in PNAS, Alnylam scientists and collaborators at the Icahn School of Medicine at Mount Sinai documented their results from studies performed in a mouse model of AIP. Prophylactic administration of an ALAS-1 specific siRNA completely protected AIP mice from phenobarbital-induced up-regulation of hepatic ALAS-1 mRNA and protein, as well as the resulting accumulation of the neurotoxic ALA and PBG heme biosynthesis precursors. This protective effect was dose responsive and durable, with a single dose administration resulting in a protective effect that lasted for at least two weeks. This feature provides an advantage over prophylactic hemin - the current standard of care in AIP - which is infused as often as twice a week in patients with frequent attacks. Further, in a treatment model, a single dose of ALAS-1 siRNA rapidly reduced the high levels of plasma ALA and PBG that were elevated during a phenobarbital-induced acute attack. In addition, preliminary comparative studies show that ALAS-1 siRNA administration was more effective than heme administration in the treatment of an acute attack, as seen by the more extensive and rapid lowering of both ALA and PBG with its administration. New results from rotarod studies showed that treatment with an ALAS-1 siRNA was associated with a significant improvement in performance as compared with animals treated with a control siRNA, suggesting that treatment with the drug can protect against symptoms of neuromotor impairment associated with AIP attacks. Finally, data were shown demonstrating that administration of ALAS-1 siRNA was not associated with a hepatic heme deficiency or altered liver hemoprotein activity.
"AIP is caused by an inherited deficiency in porphobilinogen deaminase that can result in accumulation of toxic intermediates in the heme biosynthesis pathway. Patients with AIP present with acute, and at times recurrent attacks that are characterized by severe abdominal pain, peripheral and autonomic neuropathy, neuropsychiatric manifestations, and in very severe cases paralysis and respiratory failure," said Robert J. Desnick, M.D., Ph.D., Dean for Genetics and Genomic Medicine and Professor and Chair Emeritus of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City. "Our pre-clinical work in a mouse model of AIP has shown that RNAi-mediated silencing of ALAS-1 results in rapid and effective normalization of the toxic heme biosynthesis intermediates ALA and PBG that cause the symptoms and pathophysiology of the disease. In addition, treatment with ALAS-1 siRNA in the model led to more rapid and effective lowering of ALA and PBG than a single hemin infusion, which is the standard of care for patients who have acute hepatic porphyria attacks. We have also now shown that RNAi knockdown of ALAS-1 improves the neuromotor impairment associated with acute attacks, and is not associated with a hepatic heme deficiency."
"RNAi therapeutics are promising as a novel treatment for AIP, and the other acute hepatic porphyrias, where there is a clear need for new therapies," said Makiko Yasuda, M.D., Ph.D., Assistant Professor in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City. "We look forward to continuing our very close collaborative efforts with Alnylam on the advancement of this program to the clinic."
Alnylam is currently advancing ALN-AS1, a subcutaneously administered RNAi therapeutic targeting ALAS-1 for the treatment of porphyria, including AIP. ALN-AS1 utilizes the company's proprietary Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability, and a wide therapeutic index. ESC-GalNAc conjugates are a clinically validated platform based on recent results from the company's ALN-AT3 program in a Phase 1 study. At the 9th Annual Meeting of the Oligonucleotide Therapeutics Society in October 2013, the company presented results in non-human primates (NHP), showing that multi-dose administration of an ESC-GalNAc-siRNA targeting ALAS-1 led to rapid, dose-dependent, and long-lasting knockdown of the ALAS-1 mRNA in NHPs, with an ED50 of approximately 1.25 mg/kg. Further, in a rat model of AIP, ALN-AS1 administration at doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced over-production of PBG and ALA, the toxic heme intermediates in AIP. Alnylam is currently conducting additional studies with ALN-AS1 and expects to file an Investigational New Drug (IND) application or IND equivalent in late 2014 or early 2015.
Dr. Robert Desnick and Dr. Makiko Yasuda are named with Alnylam Pharmaceuticals as co-inventors on a pending patent covering compositions and methods for inhibiting the ALAS-1 gene. In addition, Dr. Desnick receives financial compensation as a consultant for Alnylam Pharmaceuticals, and owns equity in Alnylam Pharmaceuticals in the form of stock options.
About Acute Intermittent Porphyria
Acute intermittent porphyria (AIP) is an ultra-rare autosomal dominant disease caused by loss-of-function mutations in porphobilinogen deaminase (PBGD), an enzyme in the heme biosynthesis pathway. Exposure of AIP patients to certain drugs, dieting, or hormonal changes can trigger strong induction of aminolevulinic acid synthase-1 (ALAS-1), another enzyme in the heme biosynthesis pathway, which can lead to accumulation of heme intermediates upstream of PBGD that precipitate attack symptoms. Patients with AIP can suffer acute and/or recurrent life-threatening attacks with severe abdominal pain, peripheral and autonomic neuropathy, neuropsychiatric manifestations, and possibly death if left untreated. Approximately 5,000 patients in the U.S. and Europe suffer acute porphyria attacks annually, and approximately 500 patients are afflicted with recurrent debilitating attacks. Treatment options for AIP patients suffering from an acute attack are limited; patients are treated with intravenous heme analogues that have a slow onset and can result in severe thrombophlebitis and iron overload. Currently there is no approved prophylactic treatment available to prevent recurrent attacks, which often occur monthly in women associated with menses. There exists a significant need for therapies for AIP patients.
About GalNAc Conjugates and Enhanced Stabilization Chemistry (ESC)-GalNAc Conjugates
GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology enables subcutaneous dosing with increased potency and durability, and a wide therapeutic index. This delivery platform is being employed in several of Alnylam's genetic medicine programs, including programs in clinical development.
About LNP
Alnylam has licenses to Tekmira LNP intellectual property for use in RNAi therapeutic products using LNP technology.
About RNAi
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics as genetic medicines, including programs as part of the company's "Alnylam 5x15TM" product strategy. Alnylam's genetic medicine programs are RNAi therapeutics directed toward genetically defined targets for the treatment of serious, life-threatening diseases with limited treatment options for patients and their caregivers. These include: patisiran (ALN-TTR02), an intravenously delivered RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR for the treatment of ATTR in patients with TTR cardiac amyloidosis, including familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA); ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders (RBD); ALN-CC5, an RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases; ALN-AS1, an RNAi therapeutic targeting aminolevulinic acid synthase-1 (ALAS-1) for the treatment of hepatic porphyrias including acute intermittent porphyria (AIP); ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the treatment of beta-thalassemia and iron-overload disorders; ALN-ANG, an RNAi therapeutic targeting angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia; ALN-AC3, an RNAi therapeutic targeting apolipoprotein C-III (apoCIII) for the treatment of hypertriglyceridemia; and other programs yet to be disclosed. As part of its "Alnylam 5x15" strategy, as updated in early 2014, the company expects to have six to seven genetic medicine product candidates in clinical development - including at least two programs in Phase 3 and five to six programs with human proof of concept - by the end of 2015. Alnylam is also developing ALN-HBV, an RNAi therapeutic targeting the hepatitis B virus (HBV) genome for the treatment of HBV infection. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and Genzyme, a Sanofi company. In March 2014, Alnylam acquired Sirna Therapeutics, a wholly owned subsidiary of Merck. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 200 peer-reviewed papers, including many in the world's top scientific journals such as NatureNature MedicineNature BiotechnologyCell, the New England Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.
About "Alnylam 5x15™" and Genetic Medicines
The "Alnylam 5x15" strategy, launched in January 2011, establishes a path for development and commercialization of novel RNAi therapeutics as genetic medicines. Alnylam's genetic medicine programs are RNAi therapeutics directed toward genetically defined targets for the treatment of diseases with high unmet medical need. These programs share several key characteristics including: a genetically defined target and disease expressed in the liver; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam RNAi platform with clinically proven delivery to the liver; the opportunity to monitor an early biomarker in Phase 1 clinical trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. As updated in early 2014, the company expects to have six to seven genetic medicine product candidates in clinical development - including at least two programs in Phase 3 and five to six programs with human proof of concept - by the end of 2015. The "Alnylam 5x15" programs include: patisiran (ALN-TTR02), an intravenously delivered RNAi therapeutic targeting transthyretin (TTR) in development for the treatment of TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR in development for the treatment of ATTR in patients with TTR cardiac amyloidosis, including familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA); ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) in development for the treatment of hemophilia and rare bleeding disorders (RBD); ALN-CC5, an RNAi therapeutic targeting complement component C5 in development for the treatment of complement-mediated diseases; ALN-AS1, an RNAi therapeutic targeting aminolevulinic acid synthase-1 (ALAS-1) in development for the treatment of hepatic porphyrias including acute intermittent porphyria (AIP); ALN-PCS, an RNAi therapeutic targeting PCSK9 in development for the treatment of hypercholesterolemia; ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 in development for the treatment of beta-thalassemia and iron-overload disorders; ALN-ANG, an RNAi therapeutic targeting angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia; ALN-AC3, a subcutaneously administered RNAi therapeutic targeting apolipoprotein C-III (apoCIII) for the treatment of hypertriglyceridemia; and other programs yet to be disclosed. In 2014, Alnylam and Genzyme, a Sanofi company, formed a multi-product geographic alliance on Alnylam's genetic medicine programs. Specifically, Alnylam will lead development and commercialization of programs in North America and Europe, while Genzyme will develop and commercialize products in the rest of world. In addition, Alnylam and Genzyme will co-develop and co-commercialize ALN-TTRsc in North America andEurope.
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-AS1 for the treatment of porphyria including acute intermittent porphyria (AIP), its expectations with respect to timing, and success of its clinical trials, including with ALN-AS1, its expectations regarding the potential market opportunity for ALN-AS1, its expectations regarding its "Alnylam 5x15" product strategy, and its plans regarding commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Alnylam's ability to manage operating expenses, Alnylam's ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for its product candidates, which may not support further development of product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation to update any forward-looking statements.

Friday, July 24, 2015

Thank you each and every member of the APF. We could not do it without YOU!

Thank you each and every member of the APF.  
We could not do it without YOU!


Look at all the research projects, advancements toward new medications, and people living long healthier lives.  Thank you for getting the word out to your Doctors, RN's, Family and Friends.

To the hospitals, ED's, Dr. offices with your Patient packets, Doctors receiving the Dr Kits and ER Kits.  We need you to continue speaking up about Porphyria how are you affected daily by it.

Look at all the media attention all around the world- keep speaking up and out loud!

Take a minute and ask yourself where did I get this information from, have I myself read it and educate myself and loved ones to.  I enjoy receiving gifts "golden nuggets" of information from the APF.  

I make sure that I once a year or more, I make sure that my membership is current to continue to receive these gifts & my donations are tax deductible.  So will you help encourage your family, friends by donating your time, efforts, and monetary donations to continue to support the APF.  If you have just 5 minutes a simple phone call will do so much good.  Please call 1-866-APF-3635 and have a wonderful weekend to all.


                             "Remember....Research is the key to your cure!"

images of a happy weekend

Thursday, July 23, 2015

THE "MOVE IT IN THE MOONLIGHT RUN" In Bulngton, NC August 28, 2015

 THE "MOVE IT IN THE MOONLIGHT RUN" In Bulngton, NC August 28, 2015
Shawn Willis is a dynamo in everything he undertakes. He is the owner of the Chick-Fil-A stores in Burlington, NC.  On August 28, Shawn hosts the MOVE IT Moonlight Run from for porphyria awareness to help fund the APF educational programs. Please follow the event details and join the run:http://cfaraceseries.com/races/161/



 "Remember....Research is the key to your cure!"

Monday, July 20, 2015

Information on FB Australia Site: www.porphyria-australia.org/











If you are trying to locate a good Doctor in Australia or the Australian Porphyria Group Please note this information below.  On FB you can contact with Jennifer Bellerridge and visit: http://www.porphyria-australia.org/

For Testing Locations see below:


NSW ~ Victoria ~ South Australia ~ Western Australia


NSW

Dr Victor Poulos and A/Prof Peter Stewart
NSW Porphyria Reference Unit
Biochemistry Department,
ROYAL PRINCE ALFRED HOSPTAL
Missenden Rd
Camperdown NSW Australia 2050
Phone: (61-2) 9515 8572
Fax: (61-2) 9515 7931
Email: victor.poulos@sswahs.nsw.gov.au
Website: http://www.sswahs.nsw.gov.au/SSWPS/ToDelete/RPAH/Porphyria/

VICTORIA

Porphyrin Reference Laboratory,
Biochemistry Department,
ROYAL MELBOURNE HOSPTAL,
Cnr Grattan Street and Royal Parade,
Parkville, 3050.
Phone: (61-3) 9342 7641
This is the only recognised porphyria testing laboratory in Victoria.Samples can be collected and forwarded by commercial laboratories provided they follow the recommendations.

SOUTH AUSTRALIA

John Zoanetti
Senior Medical Scientist, Department of Genetic Medicine
WOMEN'S AND CHILDREN'S HOSPITAL
72 King William Road,
North Adelaide, SA 5006

Phone: (61-8) 8161 6732
Fax: (61-8) 8161 7100

WESTERN AUSTRALIA

Dr Ric Rossi
PATHWEST
Locked Bag 2009
Nedlands, 6909, W.A.
Phone: (61-8) 9346 2845
Fax: (61-8) 9346 3882

Friday, July 17, 2015

                                                         WELCOME all new members!

 Were so happy to have you all here. 

The APF has been very busy with research studies and we encourage you to please contact the APF about getting registered, if we want a cure we need YOU! Ask for Natalia Apf, Jessica Apf @ 1-866-APF-3635

If you would like to join the Purple Light Blog it is complimentary to join.  Learn how to handle stree and anxiety while you are sick.  How to have a great Doctors visit, being prepared to diet and exercise.  So join today at this link:  https://www.blogger.com

Have a wonderful summer weekend everyone!

Your APF Membership & Support the APF with AmazonSmile for Charitable Organizations!

Your APF Membership
We are currently working on the 4th quarter Newsletter, where you can find latest news, updates and stories from the porphyria world. Our members, who made deductible charitable contributions, will receive the fresh issue.
The APF is able to maintain our physician and patient education programs and many other services because of your support. Since we do not receive government funding, we need your support and donations. Is your membership and contact information up to date? If you have moved, please update us with your current address. Be sure to send us your email address so you can receive the E-news.

Support the APF with AmazonSmile for Charitable Organizations!
You can also support the APF through the AmazonSmile program! Amazon will donate 0.5-0.8% of the price of your eligible purchases to us, at no cost to you. Please make us your choice of a charitable organization, support the research while shopping!
Please note, the program will only be available to shoppers who visit Amazon via a special web address - smile.amazon.com - instead of the normal Amazon.com homepage.
It is easy and free, AmazonSmile is the same Amazon you know. Same products, same prices, same service. Thank you for supporting us!
Please follow the link to get started: http://smile.amazon.com/ch/36-4401266



"Remember....Research is the key to your cure!"

Wednesday, July 15, 2015

Important Post *** Tests for Porphyria Diagnosis***

Tests for Porphyria diagnosis
The porphyrin precursors ALA and PBG and porphyrins are readily measured in urine. Normal urine contains appreciable amounts of these substances, and different individuals may have widely different levels. It must also be remembered that "normal ranges" do not necessarily include all normal people. Therefore, small increases, especially in porphyrins, are not always significant.
ALA is an amino acid, and PBG is a pyrrole. Both are colorless, but when present in large amounts in a solution such as urine, PBG can spontaneously form uroporphyrin, which is reddish, and other products that are brownish.
The Mauzerall-Granick method and variations of that method are preferred for measuring ALA and PBG and have been available for many years. The test involves first separating ALA and PBG from each other and from interfering substances in urine, and converting ALA to a pyrrole. Ehrlich's reagent, which reacts with pyrroles (and some other chemicals) to make a colored substance that is readily seen, is added, and the color is measured separately for both ALA and PBG with an instrument called a spectrophotometer. The Watson-Schwartz test and the Hoesch test are qualitative tests (result either positive or negative) for PBG that also use Ehrlich's reagent; they may lead to false positive results if the person doing the test lacks experience in interpretation. These two tests are rarely used if at all. If a qualitative test is positive, a quantitative assay should be done later on the same sample.
Because PBG is generally so strikingly increased during an attack of acute Porphyria, quantitation even on a spot sample (rather than a 24 hour collection) is highly informative. Requiring a 24 hour urine collection for quantitative measurements during an attack may result in considerable delay in confirming the diagnosis. Furthermore, ALA and PBG may drop considerably (especially in HCP and VP) if there is a delay of several days in collecting a 24 hour urine.
In HCP and VP, urinary porphyrins generally remain increased longer after an acute attack than do ALA and PBG. Therefore, screening for acute porphyrias should probably include measurement of total urinary porphyrins. However, it needs to be kept in mind that nonspecific increases in urinary porphyrins are common.
Measurement of PBG in serum is useful when acute Porphyria is suspected and urine cannot be collected—for example in patients with kidney failure. Serum PBG is increased in serum in the acute porphyrias, although when kidney function is normal, the concentrations are lower than in urine.
Porphyrins are tetrapyrroles (composed of four pyrroles). Porphyrins in their oxidized forms are reddish in color and are also fluorescent. Fluorescent substances, when exposed to light at certain wavelengths, emit light with a different wavelength. Porphyrins appear intensely red when exposed to long-wave ultraviolet light (UV-A). This makes them visible with a Wood's lamp, and enables them to be measured accurately with a spectrofluorometer. Within cells, all porphyrins that are intermediates in the heme biosynthetic pathway, with one exception, are in the reduced form, and are colorless and nonfluorescent. The last intermediate, protoporphyrin, is an oxidized porphyrin. Porphyrins that leave the cells and appear in blood, urine and feces are mostly oxidized and appear reddish to the naked eye and are fluorescent.
The total amount of porphyrins in a urine sample is easily measured. This is a useful test for screening especially when combined with ALA and PBG. But an increase in urine porphyrins is nonspecific, and may not be an indication of an acute Porphyria if ALA and PBG are normal.
A variety of porphyrins are present in urine. When there is an increase, particularly a large increase, in total urine porphyrins, it is often useful to determine the individual porphyrins found in urine. It is seldom important to do this if the total in normal.
The most common method for separating the individual porphyrins is "high performance liquid chromatography" (HPLC). This method will measure amounts of porphyrins with 4 or more carboxyl groups found in urine (see Table 3). In interpreting HPLC results, it is most useful to see which porphyrins predominate rather than focus on the amounts of each porphyrin.
Table 3. Porphyrin names and the corresponding number of carboxyl groups
Carboxyl groups make the porphyrin more soluble in water. Porphyrins with less than 4 carboxyl groups are not found in appreciable amounts in urine. The less soluble porphyrins with 2-3 carboxyl groups are excreted mostly in bile and feces. Coproporphyrin is excreted by both routes.
Porphyrin names Number of
carboxyl groups
Uroporphyrin (octacarboxyl porphyrin) 8
Heptacarboxyl porphyrin 7
Hexacarboxyl porphyrin 6
Pentacarboxyl porphyrin 5
Coproporphyrin (tetracarboxyl porphyrin) 4
Harderoporphyrin (tricarboxyl porphyrin) 3
Protoporphyrin (dicarboxyl porphyrin) 2
Coproporphyrin predominates in normal urine. An increase in total urine porphyrins with a predominance of coproporphyrin is seen especially in HCP and VP. But this finding alone is very nonspecific, because increases in urine porphyrins and especially coproporphyrin are common in many medical conditions such as liver diseases, bone marrow disorders and lead poisoning. Therefore, increases in urine coproporphyrin are often not due to Porphyria.
When total urine porphyrins are increased due to PCT or HEP, the increase is predominantly accounted for by uroporphyrin and heptacarboxyl porphyrin. Hexa- and pentacarboxyl porphyrin are increased to a lesser degree. These increases are understandable, because the corresponding reduced porphyrins are, in sequence, substrates for UROD, the enzyme that is deficient in PCT and HEP (Table 1). The enzyme removes 4 carboxyl groups from uroporphyrinogen one at a time to form coproporphyrinogen. Therefore, uroporphyrinogen and the intermediates with 7, 6, and 5 carboxyl groups also accumulate when the enzyme is markedly deficient. Adding to the complexity of the porphyrins in PCT is a series of porphyrins called isocoproporphyrins, which result from the next enzyme in the pathway acting on pentacarboxyl porphyrin.
The body makes primarily the isomer III type of porphyrinogens, because only these are precursors of heme. But some isomer I porphyrinogens are made in small amounts and are excreted. HPLC detects the different isomers, which adds even greater complexity. The isomer I porphyrins predominate in urine (as well as erythrocytes, plasma and feces) in CEP, because of the marked deficiency of the enzyme UROS.
Sodium carbonate (5 grams, added to a 24 hour urine bottle prior to collection) is widely recommended for urine specimens intended for measurement of PBG and porphyrins. It is widely recommended that acid be added to containers for collection of urine in which ALA is to be measured, because ALA is more stable in acid. This may be suitable if only ALA is to be measured as, for example, in screening for lead poisoning. Unfortunately, acid conditions enhance degradation of PBG, and it is seldom important to measure only ALA. Therefore, if Porphyria is suspected, sodium carbonate rather than an acid should be used, because it will be important to measure PBG and possibly porphyrins, as well as ALA, in the sample.
Fecal Porphyrins
Total fecal porphyrins are markedly increased especially in active HCP and VP and to a lesser extent in PCT and EPP. Fecal porphyrins can be separated and measured individually by HPLC. Porphyrins with 2-4 carboxyl groups generally predominate in feces. These are excreted by the liver into the bile and then flow into the intestine.
As with urine, it is most useful to measure the total amount of porphyrins in a fecal sample. If this is increased, then the laboratory should determine by HPLC which porphyrins predominate rather than focus on the amount of each porphyrin. Fecal porphyrin determinations may be confounded by variations in fecal flow; most people have one or a few bowel movements daily and a "24 hour stool collection" is really not uniform from day to day. Substances in the diet and any internal bleeding into the stomach or intestines may also interfere.
Blood tests—plasma or serum
Plasma (or serum) total porphyrins. Normally there are only trace amounts of porphyrins in plasma, and the amounts increase markedly in patients with cutaneous porphyrias. This is a very useful and underutilized test when a porphyria is suspected as a cause of photosensitivity. Being both sensitive and specific, it is increased in any patient with skin problems related to any type of Porphyria and is seldom increased in other conditions.
The preferred method, at least for screening, involves diluting plasma with a nonacid, neutral buffer and measuring the porphyrins directly by fluorescence scanning. This can serve not only as a rapid screening method for all cutaneous porphyrias but can determine whether a patient has VP rather then PCT and other porphyrias that can cause blistering skin lesions. This method also detects some cases of latent VP.
The excess porphyrins in plasma in VP are mostly covalently linked to plasma proteins and are readily detected by this method but may not be detected by the HPLC methods. It needs to be kept in mind that the normal range for plasma porphyrins is higher in patients with end-stage renal disease. Moreover, hemolysis of a blood sample invalidates a plasma porphyrin determination, because normal erythrocytes contain much larger amounts of porphyrin (in the form of Zn protoporphyrin) than does normal plasma. When the total plasma porphyrin is increased, HPLC can be used to determine which porphyrins predominate. This is done less commonly than for urine.
Plasma porphyrin measurements may be less useful for detecting EPP than other cutaneous porphyrias. One reason for this may be that protoporphyrin is very light sensitive, and the concentration in the sample can decrease rapidly if it is exposed to light during processing. Therefore, erythrocyte porphyrins should be measured if EPP is strongly suspected.
Blood tests—erythrocytes
Erythrocyte porphyrins. Normal erythrocytes, in contrast to plasma, contain appreciable amounts of porphyrins. This is almost all protoporphyrin. Therefore, erythrocyte porphyrin measurements are customarily reported as erythrocyte protoporphyrin. However, the methods can detect other porphyrins and would be more accurately described as measuring total erythrocyte porphyrins.
Because increases in erythrocyte porphyrins always almost are due to increased protoporphyrin, it is seldom necessary to separate the porphyrins in erythrocytes by HPLC. In CEP, however, isomer I uroporphyrin and coproporphyrin are usually the predominant porphyrins, as can be demonstrated by HPLC.
The protoporphyrin normally found in erythrocytes is complexed with zinc (Zn) as Zn protoporphyrin. Zn protoporphyrin increases in many conditions other than porphyrias, including iron deficiency, lead poisoning and almost any type of disorder that affects erythrocytes. Therefore, increases in erythrocyte porphyrins are not specific for porphyrias. The only condition in which free protoporphyrin (not complexed with Zn) is increased is EPP. An increased erythrocyte protoporphyrin can be shown to be due to free protoporphyrin by a simple procedure called ethanol extraction. This is useful for confirming a diagnosis of EPP.
Erythrocyte enzymes
Assays for heme biosynthetic pathway enzymes in erythrocytes, especially ALAD, PBGD and UROD, have become widely available. These assays should not be used as first-line tests for porphyrias when screening patients with symptoms. They are useful for family studies, when it is established that an index case has a particular enzyme deficiency. Difficulties with these assays in clinical practice include the following: (i) Ranges for a particular Porphyria and normals may overlap. (ii) Some mutations may cause a particular enzyme to be deficient only in nonerythroid tissues. (iii) Falsely low values are common due to problems with collecting or transporting the sample. Some laboratories employ coupled enzyme assays that may lack specificity. If a patient is found to have a deficiency of more than one enzyme in erythrocytes, it is likely that the results are not reliable.
DNA tests
Specific mutations can be identified by DNA testing. This may be the ultimate means of confirming a diagnosis of Porphyria. Once a mutation is identified in a family, this is the most reliable means of detecting other carriers of the same porphyria associated mutation.
Not every family with a given type of porphyria has the same mutation. For example, more than 200 different mutations have been identified in the PBGD gene in different AIP families. No single test for all of these DNA variations is available. Therefore, DNA testing is not suitable for screening for porphyrias, except within families.
Furthermore, not all DNA variations cause the enzyme product to be impaired and lead to a disease. Therefore, a new mutation requires further research work in the laboratory to show that it impairs the enzyme product. For these reasons, DNA testing is most meaningful only after standard testing for Porphyria has confirmed a diagnosis.

    



"Remember....Research is the key to your cure!"