text:
Wheat as a brand was founded in Denmark by Peter and Charlotte Galsgaard who as parents of young children recognized that there was a need for quality children's clothing for both fashion conscious children and their parents. There are many different brands of children clothes but the driving force for Wheat was for individuality and affordable prices in a quality driven brand.
Title | Description | Price | |
Wheat Striped Knit Pullover |
Elevate a simple outfit with this cool striped pullover in a classic green and blue stripe.... |
$80.00 | |
Wheat Knit Pullover |
Simple and cool, this dark grey knit pullover is the perfect layering item for Fall and Winter... |
$80.00 | |
Wheat Bonded Sweatshirt |
Steel grey and black stripes across this soft cotton hoodie make a bold statement. ... |
$69.00 | |
Wheat Anya Dress |
This gorgeous flutter sleeve dress in dreamy powder pink is sweet and sophisticated. The... |
$69.00 | |
Wheat Agny Dress |
Your little girl will look sweet and sophisticated in this beautiful cap-sleeve empire waist... |
$64.00 | |
Wheat Adele Dress |
Absolutely beautiful long-sleeve dress in a soft floral print. Stunning pintuck detail... |
$64.00 | |
Wheat Mathis Chino |
Dark blue chinos that go with everything--dress them up or go casual, you can't go wrong... |
$64.00 | |
Wheat Aretha Dress |
An absolutely gorgeous dress for your little girl in a soft plum hue. Simplicity is the... |
$59.00 | |
Wheat Ena Skirt |
Sweet and sassy, this adorable pleated skirt in a neutral stone shade features a whimsical... |
$59.00 | |
Wheat Classic Cardigan |
Interesting details set this classic layering piece apart. Crochet trim detailing,... |
$58.00 |
- 1 of 3
- Next


text:
The Navarre High School NJROTC Unit was selected as the best unit in Area 8 that encompasses 51 units in Alabama, Arkansas, Florida, Louisiana, and Mississippi.
"I am proud to say that you guys are Area 8's top unit!" NHS Principal Brian Noack told the NROTC cadets during an assembly of the unit.
Before the announcement, the cadets were unaware they had been selected as the number one unit in the area.
For the complete story, see the May 2 issue of Navarre Press or subscribe online.

subset: commoncrawl


text:
Garden Favors
Floral Patterned Favor Boxes
Irises, buttercups, and more flora decorate this favor box with the window to the treats inside. Choose your favorite to fill this springtime thank you. Each favor box measures 2.5"x 1.5"x 4.75" in size. Includes 2.25"x 6" gusseted cello bag with twist ti Limited quantity. Total number of boxes available: 26 Learn MoreRegular Price: $1.09
Now only: $0.75
Sunflower Medallion Cellophane Favor Bag Kit
Bright yellow sunflowers on assorted colored backgrounds decorate these milk chocolates. Spread your gratitude with cheery favors full of sunshine. Learn More -
Foil Wrapped Chocolate Sunflower Medallion
Your sunflower obsession has gone chocolate! Fill your favor boxes or bags with vivid colors of foil-wrapped sunflowers that look gorgeous and taste delicious. Learn More -
Daisy Cellophane Favor Bag Kit
A great treat for all occasions fun and romantic, leave each guest with a favor that blooms chocolate dressed up in colorful foil. Learn More$1.60 -
Butterfly Cellophane Favor Bag Kit
Hold on to these sweet favors, they may fly away. Whether you give them at a shower or a wedding, let these frivolous chocolate butterflies alight on the hearts of your guests. Learn More$1.40 -
Chocolate Butterfly
Just like the caterpillar becomes a beautiful butterfly, the two of you will become one soul. Give the memory of your wedding day to the ones you love with this sweetly carved symbol of change. Learn More$0.59 -
Distinctive Floral Design Photo Coaster Favors
These distinctive floral design photo coaster sets put an elegant photo finish on your guests' day. Learn More -
Butterfly-Design Candle Holders / Place Card Holders
Their hearts will be all aflutter when your guests are treated to these butterfly-design candle holders. Learn More -
Butterfly Design Place Card Holders
Add the beauty of the graceful butterfly to any occasion with these butterfly design place card holders. Learn More -
Foil Wrapped Chocolate Butterfly
Just like the caterpillar becomes a beautiful butterfly, the two of you will become one soul. Give the memory of your wedding day to the ones you love with this sweetly carved symbol of change. Learn More$0.80 -
Butterfly Design Curio Box Favor
A beautiful choice for any occasion, this butterfly design curio box favor is a treasure to behold. Learn More -
Butterfly Candy Dish from the Porcelain Remembrances Collection
Let your event plans take flight with this exquisite butterfly candy dish favor from the Porcelain Remembrances Collection. Learn More -
Calla Lily Design Bookmark Favors
A symbol of strength and beauty, these calla lily design bookmarks make stunning mementos of your day. Learn More -
Enchanting Bride and Groom Calla Lily Design Place Card Holder
This enchanting bride and groom design place card holder makes it easy to welcome your guests in style. Learn More -
Bride & Groom Calla Lily Design Key Chain Favors
Give your guests a little piece of your heart on your wedding day with these bride and groom design key chain favors. Learn More


text:
The World's Worst Invasive Mammals
Animals as common as goats, deer, rabbits or mice can have a devastating effect on other wildlife
- By Jess Righthand
- Smithsonian.com, December 20, 2010
Brushtail possum (© Juniors Bildarchiv / Alamy)
The brushtail possum (Trichosurus vulpecula) lives only in its native Australia and nearby New Zealand, where it was introduced in 1837 to establish a fur trade. The nocturnal marsupial is about the size of a cat and lives mostly in trees. In Australia, dingoes and bush fires keep the population in check. But in New Zealand, an environment that evolved almost completely devoid of land mammals for 65 million years, until the arrival of the Maori around 1250 A.D., the possum invasion is a very different story.
Possums are now ten times more abundant in New Zealand than they've ever been in Australia. With an absence of predators, the possums are free to roam and graze on whatever's palatable. Their feeding on eucalyptus leaves has created a large imbalance in the island forest vegetation, and the possum's appetite for birds has depleted some species like the threatened kokako bird and the kereru, a native pigeon.
"The trouble is, they're actually quite nice animals," says Mick Clout, a conservation ecologist at the University of Auckland in New Zealand. "If you see them in their native Australia where they belong, they're fantastic. But they don't really belong here [in New Zealand]."
Of utmost economic concern is that possums are the main wild vector of bovine tuberculosis, which can devastate cattle. Though the animals are still trapped for their pelts, this does not completely control the population and wildlife authorities have been forced to use other, sometimes controversial, methods, such as aerial poisoning.
Comments (38) |
It amazes me how man always puts the blame on an animal instead of himself.
Posted by Margaret Mitchell on April 12,2013 | 04:32 PM
I was surprised readinng the comments that so many people feel as I do: human beings are the problem, not feral cats. This article just gives people permission to be even more cruel to animals than we already are. I am not a Christian or anything else for that matter, but I am very familiar with the Bible and we should be stewards of this earth, not the primary destroyers. We have the judegement and ability to conrol our population, but the Smithsonian and other institutions that should be shouting out loud that there are too many people and we should do what we can to curb our numbers are doing nothing to get this message across. And they have all those researchers who make one mess after another trying to control nature in one way or another. First annhilate wolves, then reintroduce them, then start shooting them again. What happened to our intelligence and humanity? People need to spay or neuter their cats and dogs. It is that simple. If we did that, there wouldn't be feral cats and dogs who suffer pretty terrible lives. But I think that given the choice, they would choose to live, just as we would.
Posted by Sharon Logan on February 13,2013 | 09:27 AM
Man has been the cause of every problem in nature. For that matter in everything on Gods Green earth. Ive been sayin it for 30 years "There are just to many people"and yet world wide we continue to multiply into greater and greater numbers every day.
Posted by Doug on January 25,2011 | 07:51 PM
Photo#10 is a mongoose.Ohahu is covered with them.Introduced to rid the island of snakes.As far as invasive goes there are a lot of animals that aren't on the list,including humans.It depends on where you live,and how you define invasive.I'm over sixty,and I've seen a lot.I believe the earth will heal.The thing I like the best about all of the other animals,they don't have opinions.They don't pass judgements on each other,and they live within their environment.They don't try to change to suit their fancy.Wether you're a creationist or evolutionist man belongs here.I don't believe we came from outerspace.I'm a Christian and I believe we are part of God's plan.All of those"invasive" are too.I don't believe God sees them as invasive.
Posted by Don hart on January 24,2011 | 05:08 PM
I am surprised that the virgina possusm,raccoon and the rock
dove also known as pigeons. These animals had spread since the settlers had come from europe. As well the coyote from the
west to the eastern part of United States.
I known about the feral cats killing wild bird populations
as well,the domestic young duck,goose and turkeys. When I was
a younger man. I had to help thin out the feral cat population on my cousin's and neighboring farms with my 22 long rifle.
Posted by David Norris on January 23,2011 | 02:51 PM
I'm really not sure about your findings. Here in northern Wisconsin I've only seen where the more Red Squirrels you have the less Gray Squirrels you have.I've read where they actually do more damage than grays, by eating bird eggs, nesting in buildings, and actually chasing down grays when they come into their area. If I'm wrong let me know.
Posted by Dave Franzen on January 22,2011 | 09:08 PM
NUMBER ONE: Human Beings. I was really surprised you guys didn't know about this.
Posted by mimi on January 20,2011 | 10:13 AM
Posted by Heather C on January 19,2011 | 06:09 PM
I totally agree- the first guilty party here is the human race---mostly Europeans , their greed, arrogance and selfishness. there is no God that will fix this, we have to take care of the world ourselves. zMaybe we acn stop some of this, but I doubt it. Way too many humans are not in TOUCH with the earth. We are of the earth.
Posted by peggy york on January 19,2011 | 05:30 PM
You really should have included Homo sapiens in this list.
Posted by Donna Nespoli on January 16,2011 | 02:18 PM
Coyotes are overabundent here in New Your State. They have greatly reduced the deer herds by eating the fawns. There is a hunting season for them, but it doesn't seem to do much good so I guess the reproduction of coyotes is true. I don't think coyotes should be more welcome in the state than wolves who always get a bad rap due to the old stories.
Posted by Frances Osteen on January 15,2011 | 11:29 PM
The article probably ought to specify that specifically European rabbits are invasive in the Americas, given that there are plenty of native species.
Posted by Barry Schwartz on January 13,2011 | 12:26 AM
We humans supposedly have the greater adaptive ability overall. An expression of that adaptive trait would be in recognizing our environmental role and impact. At least some can acknowledge the part we've played in the invasive species introductions that caused such ecological concern. Hopefully we are adaptive enough to come up with proper solutions to the mistakes made and lay a course correction wherever possible; and more importantly, let's hope we can learn from past mistakes and not continue to repeat them.
Posted by Tony on January 11,2011 | 07:00 PM
Very nice assortment of animals here and some interesting comments. As a devoted Christian, it is our responsibility to be good stewards of the gift that God has given us. Though I think the Lord will be coming soon, we have to keep our house clean until that day. Whether you want to consider humans as invasive or not, we have needs of the resources that are here, but we should not destroy our homes (ie, the environment outside my door which includes the whole earth). It is sickening to watch areas that are livable being destroyed by greed. In the last forty years or so, we have doubled from 3.5 billion people to 7 billion people. Everyone of them is or was someones darling baby (or grand baby). Let's manage the world so that all of God's children (those alive today and those coming in the future) can enjoy a wonderful world.
Posted by Wayne Youngquist on January 8,2011 | 02:23 PM


text: Road Dawgs Place Ozarks Region View Website Calculate Trip Get Directions Overview:Great selection of biker leather; special women's section with leather skirts, pants, shorts, undies, halters and more! Jackets, vests, chaps, T-shirts, doo-rags, saddlebags, grip and leather fringe. Patches and sewing available. A great poker run stop. Address: Road Dawgs Place 528 West Van Buren Eureka Springs, AR 72632 Phone: 479-253-8474 Website: firstname.lastname@example.com E-mail: email@example.com GPS: N36.4211119 W93.7699931 Connect: Save to foursquare Miscellaneous No Smoking


text:
24/7 expert virus removal assistance with enhanced protection from online security threats. Our virus removal experts will detect, isolate, and remove all viruses and spyware from your machine. We will review your existing security plan and if needed, install & configure the latest antivirus software suite on your Computer. Firewall optimization will be performed to enhance your security defense, and finally, we will schedule automated virus, spyware, and malware scans.
Protect your computer from online threats and have security experts remove viruses from the system whenever needed, with the Award winning 24/7 computer support from AdachiCompuTech for one low price. You can choose a computer support plan that best suits your immediate need, starting at just $179.95 a year. That's a one full year of unlimited support for the price of 1 incident! Call AdachiCompuTech 24/7 and give our expert techs access to your computer via remote connectivity to have your antivirus software suite installed & configured; driver updates applied; start-up errors repaired; viruses-Trojans-spyware removed remotely. Our computer support experts are available online 24/7 to assist you.
Need an instant help for a computer problem? One-Time PC fixes are just what you need right now. If you just need an instant help with virus removal, spyware removal, software installation and set-up for your printer and/or other devices, PC Tune-Up, and more. These One-time PC Fixes start at just $45.95 Chat with a support expert to get started or call us now at 1.866.607.2321
Adachi Computech Solutions is a leading global technology support services provider, offering comprehensive 24/7 technical services to consumers and business enterprises with integrated tools that enable optimized service execution across the entire service industry. The company deploys the most widely used artificial intelligence based field service scheduling application and remote tech support connectivity suite to dispatch service professionals throughout the United States, Canada, the United Kingdom, Australia, Europe, and Africa.
AdachiCompuTech also provides outsourced Business IT Support, remote managed services, server virtualization, cloud solutions, call center services, web development, web hosting, search marketing, social media optimization, and digital content marketing services.


text:
Having a Garage or Yard Sale? Share the details here to be added to our interactive map of sales.
Later this week we'll show you a map of sales in the area. This map shows you sales in several Boston neighborhoods. You can also add your sale to your local Patch by clicking on it below:
If you're looking at this on your mobile device, switch to desktop view.


text:
AA Calibration opens new facility in Yazoo
Managing Editor
U.S. Rep. Bennie Thompson joined Yazooans Thursday in celebrating the opening of AA Calibration's new facility in the industrial park.
"Good jobs are hard to come by," Thompson said. "City and county leaders are to be congratulated for luring a business like this into the community."
Owner Larry White said his business has already been able to hire three more people than he expected since expanding from his original Main Street location.
-------for the rest of the story see The Yazoo Herald printed edition or subscribe to the Digital Edition.----------


text:
See All Brands•See All Categories
Items: 0 • $0.00
Tracking•Help•Contact Us
Retail Price: $54.06
60 caps
$7.99Save 57%
120 caps
$14.99Save 52%
Hyaluronic Acid + MSM Description from BODY FIRST Hyaluronic Acid (HA) is a compound found in the cartilage, skin and other connective tissues of the body. HA helps to hold lubricating moisture within the joints and cartilage, which affects their resilience, elasticity, and strength. MSM is a natural source of sulfur- a critical component of hair, skin and nails. MSM has also been shown to have anti-inflammatory properties.
Ingredients: Other ingredients: Gelatin, Magnesium Stearate, Microcrystalline Cellulose and Silicon Dioxide.
Manufacturer's Directions Adults, take 2 capsules per day with a meal.
Manufacturer's Disclaimer If you are pregnant, nursing or taking any prescription medication or planning any medical procedure, consult your doctor before use. Discontinue use and consult your doctor if any adverse reactions occur. Keep out of reach of children.
Title your review * (150 character max)
Share your opinion * (4000 character max)
How would you rate this?
BODY FIRST Hyaluronic Acid + MSM 60 caps
Our Price $7.99
BODY FIRST MSM (1000mg) 60 caps
Our Price $3.39
BODY FIRST Glucosamine Chondroitin MSM 240 caps
Our Price $19.99


text:
Victoria has a strange encounter with someone in the school bathroom!
Embed this Video
Tori is so stressed out by the pressure of stardom, she might just pour pasta down American Hero Buzz Aldrin's pants.
When the pressure of stardom is too much for Tori, Beck is there to be a friend...and maybe a little more.
The Hollywood Arts students try their best to impress the judges of the Platinum Music Awards.
Tori wins a competition to sing at the Platinum Music Awards! Will she 'cut the mustard' as the opening act?
Victoria Justice tells us all about Tori Goes Platinum - can you guess what happened on set?
Victoria Justice rocked some pretty crazy outfits for the filming of Tori Goes Platinum.
The story of how Trina got into Hollywood Arts is traced back to one sip of extremely old coconut milk.
When Robbie and Tori can't pay for their sushi, they stand to lose more than their lunches.
Tori Vega has the chance to become the world's next big star, but certain obstacles must first be tackled! Don't miss the brand new 1 hour Victorious special: Tori Goes Platinum, Saturday May 19th at 8/7c!
This holiday season, Nickelodeon crowns the new King of Wrap!
Get access to full episodes from all your favorite Nick shows right here!


text: Welcome! You are viewing an archived issue of SaskSecrets, Tourism Saskatchewan's Online Newsletter, from March 2009. To read the current issue of SaskSecrets, click here.2009 First Nations University of Canada PowwowThis year marks the 31st Annual Spring Celebration for the First Nations University of Canada, which features the very popular 2009 First Nations University of Canada Powwow. More than 700 dancers will compete for over $56,000 in cash prizes. From April 4 - 5, 2009, the Brandt Centre, Evraz Place in Regina, will host this much anticipated event, which is one of the biggest Powwows in Saskatchewan. It attracts more than 7,000 visitors and participants from across Canada and the United States. This celebration of spring announces new life and gives thanks for sharing in the rebirth of the land. Since it first began in 1978, the powwow has been held every year to celebrate cultural diversity, to unify families and communities, and to demonstrate First Nations traditions through a wide variety of song and dance styles. In addition to the powwow, this event also hosts a Trade Fair, Aboriginal Fashion Show and more. Click here to learn more about the 31st Annual Spring Celebration and 2009 First Nations University of Canada Powwow. All photos courtesy of First Nations University of Canada. |


text:
Rachel Welte is the Weekend News Anchor and a General Assignment Reporter.
COLORADO SPRINGS, COLO. -- An interesting story coming out of the FOX21 News studio.
Sometime overnight Sunday the server that stores our emails was hacked, and the person(s) responsible is literally holding our information for ransom, asking for $5,000 to unlock the data he scrambled.
Our engineers did some research and found this hacker hit a number of servers around the globe, but the FBI has not been able to find him because he is using ghost addresses.
FOX21 engineers were able to get the email system back up and running early Monday morning.


text:
Lumishore Thru-Hull Color Change Underwater Lights - Pair - 72W
Thru-Hull Color Change Lights - Pair
THX72-CCP-2 Color Change Controller Included The Lumishore Thru-Hull Color-Change Plus is designed for those owners who would prefer the integrity of thru-hull installation using the most powerful, efficient and cost effective underwater LED lighting systems on the market today. Available in a variety of power levels the Lumishore Thru-Hull is suitable for many sizes and types of watercraft including Sports Boats, Cruisers, Yachts, and Super Yachts where a permanent hull fixture is required. The Lumishore Thru-Hull Color-Change Plus is a desirable replacement fitting for existing underwater hull lighting systems, and is manufactured to the highest standards and is made from the finest marine grade materials. Benefits:
This product ships in 1 business day. Add to Cart and enter your Postal Code to determine the shipping charges and estimated delivery date. * Most products and orders leave our warehouse in 1 business day. However, select items may take more processing time. Alaska and Hawaii orders please add 1 additional warehouse processing day. Standard Shipping Policies
Please be careful when ordering this product, it has limitations that differ from our General 30-day Return Policy. After all, we want you to be satisfied with your order so you'll return again and again as an iboats.com customer, and to also recommend us to your boating friends


text:
This instructable will show you how to make a cheap and simple driver circuit in order to get high voltage arcs out of a component called a flyback transformer.
A flyback transformer, sometimes called a line output transformer are used in older CRT TV's and computer monitors to produce the high voltage needed to power the CRT and electron gun. They also have other auxiliary windings built into them that the TV manufacturers use to power other parts of the TV, so they are usually customised by the manufacturers.
For the high voltage experimenter they are used to make high voltage arcs, which is what this instructable will show you how to do with just a few simple electronic components.
You can get flyback transformers out of older CRT monitors and TV's. They are the ones that have a big heavy chassis. There are also other instructables on this website showing how to remove them from the chassis and circuit board.
I am in no way responsible if you mess up with this circuit. If you mess up you have no one to blame but yourself.
What you will need:
1x Flyback transformer
1x 2n3055 transistor + heatsink
1x 220 ohm 5 watt resistor
1x 22 ohm 5 watt resistor
(Note: The resistor values do not have to be exact. Say if you had a 33 ohm and a 200 ohm resistor they would still work fine for this circuit).
Some enamelled magnet wire, single core bell wire also works well too for the primary and feedback coils.
A fast diode. Although this is not needed for the circuit to work, it protects the transistor from back emf spikes and can help prolong the life of the circuit. I just used the one I found on the TV board but the UF4007 is an easy one to get hold of in electronic stores if you need to buy one.
+Some way of connecting the components
such as alligator clipped cables or wire and solder.
You may not, except with our express written permission, distribute or commercially exploit the content. Nor may you transmit it or store it in any other website or other form of electronic retrieval system.
1-40 of 129 | Next » |
I followed your instructable and made a great one :). One thing that I am wondering is the output of the driver. Is it AC or DC, what is it voltage, amp, frequency? Once I tried to measure it by a multimeter and the multimeter died :(
Is thinner or thicker gauge wire better for bigger arcs?
~ Brad
I found different flyback transformers to react differently. Some worked better with more turns whilst others did not, so experimentation is needed here.
It is more than just turns ratio that determines the size of the arc in this driver, the frequency that this self oscillating driver oscillates at will play a part. There will be a "sweet spot" that produces the biggest arcs, but at the expense of more power draw and transistor heat (mostly, but that is a whole different issue).
Adding turns will increase the inductance of the winding and thus decrease the running frequency.
Generally thicker wire is preferable but anything larger than 20-18SWG is over kill for this.
As requested I have posted some pictures to help us both out :)
The cables aren't coloured right for the polarities and the wires with blue tape is the primary coil. I am using a 2n3055 and the same heatsink as you, coincidentally. No wires are shorting to the heatsink or others.
Any questions, ask me :)
From the photos it looks like you have gotten the resistors mixed up. The 220 ohm should be installed where you currently have the 22 ohm, and the 22 ohm should be where you currently have the 220 ohm.
Try swapping them around and see if it works.
I have built one of these but there is no high pitched noise. I have tried 2 transistors and swapped the primary and feedback coils' polarity and did everything on your troubleshooting page but nothing is making a noise or outputing any arcs. I am using a PP3 battery just temporerily until it works but do you think if I used a 18v cordless drill battery it will work?
Try experimenting with using different numbers of primary and feedback turns.
Try checking for continuity between the coils and rest of the circuit as with magnet wire it is sometimes hard to get a good connection.
If you put a quarter watt resistor in there though it would be a different story (small resistor + lots of heat = flames lol).
Tried 3 different flyback transformers, 2 transistors, two different windings (7 x 11 and 5 x 20), powered from both 2 x 6V dry cells in series and also a car battery, triple checked continuity and resistance on all parts, but.... no spark! Not only no spark, no heating of the transistor, no noise, nothing. Is this a hoax?
How does this circuit create a high frequency oscillation? Why does mine create neither sparks, no noise, no noticeable heating of any component? Components: radio shack 2n3055 transistors, 220 and 22 ohm 5 watt ceramic resistors, tried with and without the diode. Any ideas?
No this is not a hoax, with it working when you first apply power to the circuit current flows through the potential dividers and into the base (which the potential dividers bias it to at around 0.8v). As the transistor begins to turn on current starts flowing through the primary coil (storing energy in the core) into the transistors collector, out of the emitter and then to ground.
But since there is the feedback winding sharing the same core current will be induced onto that too. This is why it needs to be connected in the correct polarity so that the current induced onto this winding turns the transistor off. When it does turn the transistor off the voltage across the primary coil will be now ring up to many times that of the original input voltage, and so will the secondary coil thus causing the HV.
This is also where the fast recovery diode and maybe a small capacitor help to protect the transistor.
Have you checked each individual component out of circuit? A good transistor should show about 0.7v drop between the Collector-Base and Base-Emitter junctions. If you used magnet wire for the coils then check for continuity there as sometimes not scraping enough enamel away makes for a bad connection. Also when winding the coils it can be easy to accidentally scrape of some of the enamel with the core edges and that can create shorts between windings.
Check the current draw too of the circuit and the voltage of your power sources when under load.
Hopefully you'll get it working ( :
Also have you tried reversing the primary and feedback connections?
You could get some small sparks though by manually pulsing the battery through the primary coil (although they would be very small and hard to see).
This circuit self oscillates and gives the primary coil the high frequency pulsing DC it needs to function (plus the flyback "back emf", that is the real reason for the high voltage).
1-40 of 129 | Next » |


text:
[Beowulf] real hard drive failures
Many of your questions may have already been answered in earlier discussions or in the FAQ. The search results page will indicate current discussions as well as past list serves, articles, and papers.
Mark Hahn hahn at physics.mcmaster.caTue Jan 25 14:26:36 PST 2005
- Previous message: [Beowulf] real hard drive failures
- Next message: [Beowulf] real hard drive failures
- Messages sorted by: [ date ] [ thread ] [ subject ] [ author ]
> > I'm only partially interested in the thread "Cooling vs HW replacement" but > > the problem with drive failures is a real pain for me. So, I thought I'd > > share some of my experience. > > i'd add 1 or 2 cooling fans per ide disk, esp if its 7200rpm or 10,000 rpm > disks I'm pretty dubious of this: adding two 50Khour moving parts to improve the airflow around a 1Mhour moving part which only dissipates 10W in the first place? designing the chassis for proper airflow with minimum fanage is obviously smarter and probably safer. > - if downtime is important, and should be avoidable, than raid > is the worst thing, since it's 4x slower to bring back up than > a single disk failure eh? you have a raid which is not operational while rebuilding? > - raid will NOT prevent your downtime, as that raid box > will have to be shutdown sooner or later > ( shutting down sooner ( asap ) prevents data loss ) huh? hotspares+hotplug=zero downtime. but yes, treating whole servers as your hotspare+hotplug element is a nice optimization, since hotplug ethernet is pretty cheap vs $50 hotplug caddies for each and every disk ;)
- Previous message: [Beowulf] real hard drive failures
- Next message: [Beowulf] real hard drive failures
- Messages sorted by: [ date ] [ thread ] [ subject ] [ author ]
More information about the Beowulf mailing list


text:
Office Location: 183 Physics
Office Phone: 919-660-2512
Email Address: email@example.com
Nonlinear dynamics and complex systems
BS, University of Rochester, 2007
Research Categories: Complex and Nonlinear Circuits, Ultra Wideband RF Transmission, Wave-Chaos, Sub-wavelength Imaging Techniques
Research Description: While at Duke, I have studied time-delayed feedback in oscillators in order to realize inexpensive and robust sensor systems. Conventional oscillators using time-delayed feedback use a nonlinear element whose output is amplified and coupled back to the input through a single feedback loop that delays the signal by a fixed amount. These systems can display a variety of behaviors including periodic oscillations, quasi-periodicity, and chaos. Oscillators using time-delayed feedback have been designed using high-speed commercial electronics or lasers to generate complex signals with frequency bandwidths that stretch across several gigahertz. My current research goals are to understand and exploit the broadband nature of such devices to realize sub-wavelength and other radio-frequency sensing techniques. In line with these goals, I am currently working on several experiments that utilize the complexity of the dynamics from nonlinear time-delayed feedback oscillators.
Representative Publications


text:
Technological innovations are outpacing traditional backup methods such as tape, disk, and strict NAS devices, leaving IT managers searching for better solutions that go beyond data protection to deliver:
That's where intelligent business continuity comes in.
Check out this quick data sheet to examine a side-by-side comparison of the capabilities of traditional backup vs. intelligent business continuity. You'll notice a stark contrast in each of ten critical backup categories.


text:
The ancient people measured time in cycles called "baktuns" of 394 years each, and the winter solstice coming Friday marks the end of the 13th baktun. Some who study the calendar say the date for the end of the period is not Friday, but Sunday.
The Mayan calendar is based on the position of the heavenly bodies -- the sun, the moon and the stars -- and was meant to tell the Mayan people about agricultural and economic trends, said archeologist Alfredo Barrera.
NASA is also weighing in on the matter, with a post on its website declaring that the world will not end on Friday.
"It will be another winter solstice," NASA said. "The claims behind the end of the world quickly unravel when pinned down to the 2012 timeline."
As of Thursday afternoon in the eastern United States -- already Friday across Asia -- the space agency said it had detected "nothing unusual" and that it anticipated a normal couple of days ahead.
The hubbub about a calamity occurring comes from a Mayan stone carving called monument 6, made in 700 A.D., which predicts a major event at the end of this baktun, Barrera said. But half of the broken tablet is missing, so one may only speculate on what the complete message may be.
Whatever it is, it's not about the end of the world, he said.
"We don't have a prophecy or inscription related to the finish of the world. It just mentioned a deity."
Barrera said he believes the hullabaloo about the end of the world has been whipped up by online speculation -- and he finds it a bit ignorant.
In Merida, Mayan priest Valerio Canche conducts an ancient ritual to honor the dead in light of the upcoming end of the 13th baktun.
"It is considered the closure of the great cycle of Mayan time," he said. "But, of course, the cycle (14th baktun) begins the following day. For the Mayans, it's not the end of the world."
If you're reading this on Thursday, keep in mind that it's already Friday in New Zealand, and it's still on the map. If it's Friday, a look out the window may be reassuring.
If it's Saturday, and no major calamity has occurred, then relax and go celebrate the beginning of the 14th baktun with the Mayans.


text:
Hi there everyone my name is Alice :)
I am new to this site but not to roleplaying, and would really like to meet some like minded people in which to experience some wonderful Roleplaying Fun! :) I am not very good with introductions so I might as well just go straight into some details about myself. I am currently 22 years of age and I am studying Law at University. The types of Roleplay's that I like to do include School-themed, Anime-styled, Fantasy, Action, Adventure and I am a sucker for Romance. I also don't mind darker themes, and will consider roleplaying mature themes with the right person.
Anyway enough about me I want to hear all about you guys! ^.^ Please hit me up for a chat if you are bored, or if you need an extra member in your Roleplay please count me in :)
I look forward to getting to know all of you! ^.^


text:
The Tennessee Department of Education is now in the final year of a five year federal Charter Schools Program (CSP) grant. The grant ends in July 2014. Tennessee recently awarded $3,600,000 in planning and implementation grant funds to twelve authorized charter schools to use in 2012-13 and 2013-14. Grants are awarded through a peer reviewed competition.
The department will run a competition in August 2013, for applicants authorized by that time. Another competition will be run in November 2013 for any applicants authorized following an appeal to the State Board of Education. These competitions are for schools authorized in the April 2013 cycle, planning to open in 2014. Those schools may apply for $150,000, to be used during the planning period ending July 31, 2014.
The U.S. Dept. of Education may or may not have additional grant funds that Tennessee could apply for when our current grant ends in July 2014.
The U.S. Dept. of Education's entire budget allocated to charter school programs has shrunk in recent years. At the same time, the Department has been offering more grants directly to charter schools and networks, as well as to national foundations supporting the growth of charter schools. In Tennessee, charter school sponsors may be able to apply for several different grants, such as these:
In 2013, this Lipscomb University study examined the best uses of Charter School Program (CSP) grant funds.
In addition, there are many more organizations investing in promising or successful charter school programs (e.g., the Tennessee Charter School Incubator, Partners for Developing Futures).
Application Documents |
Planning & Implementation (PLIMP) Grant Application 2013 |
Planning & Implementation (PLIMP) Budget 2013 |
Planning & Implementation (PLIMP) Scoring Rubric 2013 |
Applicant Webinar Materials - Aug. 2013 | ||
Reconciliation Documents |
Reimbursement Instructions (2012) | |
Itemized Expense Documentation | ||
Reimbursement Request Form |


text:
Hello all!
As some of you know, Duke is able to provide a live stream video of the Divinity Baccalaureate service for those with loved ones who cannot attend. Please see instructions below:
For the live stream on Saturday night May 11th beginning at 6:30 pm:
- Go to the Duke Chapel web site at http://www.chapel.duke.edu/
- Then click on blue box on the right side of the page "Live Stream" http://www.chapel.duke.edu/flash/flash.html and the Divinity Baccalaureate should pop up ready to go at 6:30 pm.
To watch the service after the event is over:
- Go to the Duke Chapel web site, http://www.chapel.duke.edu/
- Click on the "Live Stream" box, and underneath you will see options. Click on "Video Gallery" or go to the left hand side of the page in the light blue boxes and click on "Duke Chapel I-Tunes". Both of these lead you to the archives: http://www.chapel.duke.edu/multimedia/video.html.
- Search for 'Divinity School Baccalaureate, Saturday, May 11 at 6:30 pm.' Be aware there are files for other University Baccalaureate services archived, you want the Divinity School Baccalaureate.


text:
Jackie Bird and Wee Willy's raise funds for CASA
On Saturday evening Wee Willy's in Marblehead was packed and lively.
On Saturday evening Wee Willy's in Marblehead was packed and lively.
The BCS Board of Education approved a 5-year financial forecast on Tuesday, October 23rd that puts forth an end to the deficit spending that has plagued the district for the past 4 years.
On Saturday, Oct. 20h, the Oak Harbor FFA Chapter held their first community service project, "Raking the Leaves."
The Mental Health & Recovery Board of Erie and Ottawa Counties hosted its 18th annual awards for excellence banquet the evening of Oct. 30 at the Sandusky State Theatre.
On Oct.24, prior to the student and parent open house at Port Clinton
Middle School, Chris Harris and Joanna Russell from Port Clinton Walmart
visited with the staff. They brought a cake and goody baskets to share.
Through the Walmart Teacher Rewards program, they also had a drawing for
$50 gift cards for a few lucky staff members.


text:
looks pretty good! -
Post a comment
99 Comments
mattwalks said 252 weeks ago
totally horrible.
I don't even get the connection. Tony Montana? Al Pacino? Scarface? To George Washington?
No. Sorry. -
eludingsun said 252 weeks ago
*sigh* i agree with snarkygal and undertow976. i was especially disappoint with the "tell us a little about this design".
i was pretty content the last few days thinking the bad reviews had been taken into consideration. but once again, i'm disappointed.. this site did start off so well... -
eludingsun said 252 weeks ago
or as my boyfriend is saying behind me:
"wow that's NOT funny. honestly, whoever created that, just showed how ignorant they are." -
sdguy1103 said 252 weeks ago
it's cool---all in good fun I'm sure. Definitely a shirt that will get attention...a good thing!
some people should just lighten up! Schweettt! -
lvytn said 252 weeks ago
Heh my first tee fury purchase. Although now I feel like a smurf after reading everyones comments.. :p -
Kempera said 252 weeks ago
Going to be my first too :D
It's ok though, like sdguy said, people should lighten up. -
verilens said 252 weeks ago
Nice design :) Not really sure how it's "ignorant." I'm not into humor shirts myself, but I think people are being atypically harsh on this one. Lighten up, people! There will always be another design tomorrow...
The animal tee on the sidebar is A++ awesome. -
DCAY said 252 weeks ago
Come on people, lighten a little... Tis just a joke and nothing more, and of course not everyone's cup of tea. Don't hate on this site for allowing artists to make their work available to the masses... at least those enjoy stupid humor. -
snarkygal said 252 weeks ago
I'm wondering if its even legal to use art from money for other purposes... and the face and backing is a direct lift -
MJ said 252 weeks ago
Part of the beauty of TeeFury is the variety- sorry some folks aren't digging this one, but there's always tomorrow. And the day after that. And the day after that. ;) -
Wax Doll said 252 weeks ago
His reason behind the design makes sense. I don't think it's ignorant in any way. The artist has his own way of expressing his art, so cut him some slack and give constructive criticism even if you don't like it. -
RawkHeroin said 252 weeks ago
I really dig the concept. A lot. Not 100% on the execution, though. Just my $.02. -
necrophyte said 252 weeks ago
Heroin's right. Love the idea, but the art's kinda, er, "inconsistent," in a sense. -
hjdttt said 252 weeks ago
To us, the father of our country. To the British, he was a rebel, even an A-hole. If he lived in the 21st century, might he not be toting a semiautomatic?
OK, it's a little fast and loose with the reinterpretation of history, but the artist has that vision and the right to that vision. If Washington and Lincoln are sacrosanct to you, buy some other T. Personally this reminds me of Patty Hearst in the Symbionese Liberation Army. -
MJ said 252 weeks ago
Personally, I saw the gun as a statement on the cutthroat approach many in this country have to capitalism, not a statement on George Washington so much as on money itself. So I think the design is fairly open to interpretation. - Load More Comments
Have a Facebook account?
Connect with Facebook
What is this?


text:
Lipoic acid
Lipoic acid | |
(R)-5-(1,2-dithiolan-3-yl)pentanoic acid |
Other names
α-Lipoic acid (alpha lipoic acid); Thioctic acid; 6,8-Dithiooctanoic acid |
Identifiers | |
CAS number | 1200-22-2 (R) , 1077-28-7 (racemate) |
PubChem | 6112 |
ChemSpider | 5886 |
DrugBank | DB00166 |
MeSH | Lipoic+acid |
ChEBI | CHEBI:30314 |
ChEMBL | CHEMBL134342 |
ATC code | A16 |
Jmol-3D images | Image 1 |
Properties | |
Molecular formula | C8H14O2S2 |
Molar mass | 206.33 g mol−1 |
Appearance | Yellow needle-like crystals |
Solubility in water | Soluble as sodium salt |
Solubility in ethanol | Soluble |
Pharmacology | |
Bioavailability | 30% (oral)[1] |
Related compounds | |
Related compounds | Lipoamide Asparagusic acid |
(verify) (what is: / ?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
Infobox references |
Lipoic acid (LA), also known as α-lipoic acid[2] and alpha lipoic acid (ALA)[3] is an organosulfur compound derived from octanoic acid. LA contains two sulfur atoms (at C6 and C8) connected by a disulfide bond and is thus considered to be oxidized although either sulfur atom can exist in higher oxidation states. The carbon atom at C6 is chiral and the molecule exists as two enantiomers (R)-(+)-lipoic acid (RLA) and (S)-(-)-lipoic acid (SLA) and as a racemic mixture (R/S)-lipoic acid (R/S-LA). Only the (R)-(+)-enantiomer exists in nature and is an essential cofactor of four mitochondrial enzyme complexes.[4] Endogenously synthesized RLA is essential for aerobic metabolism. Both RLA and R/S-LA are available as over-the-counter nutritional supplements and have been used nutritionally and clinically since the 1950s for various diseases and conditions. LA appears physically as a yellow solid and structurally contains a terminal carboxylic acid and a terminal dithiolane ring.
The relationship between endogenously synthesized (enzyme–bound) RLA and administered free RLA or R/S-LA has not been fully characterized but free plasma and cellular levels increase and decrease rapidly after oral consumption or intravenous injections. "Lipoate" is the conjugate base of lipoic acid, and the most prevalent form of LA under physiologic conditions. Although the intracellular environment is strongly reducing, both free LA and its reduced form, dihydrolipoic acid (DHLA), have been detected in cells after administration of LA. Most endogenously produced RLA is not "free" because octanoic acid, the precursor to RLA, is bound to the enzyme complexes prior to enzymatic insertion of the sulfur atoms. As a cofactor, RLA is covalently attached by an amide bond to a terminal lysine residue of the enzyme's lipoyl domains. One of the most studied roles of RLA is as a cofactor of the pyruvate dehydrogenase complex (PDC or PDHC), though it is a cofactor in other enzymatic systems as well (described below).
Biosynthesis and attachment[edit]
The precursor to lipoic acid, octanoic acid, is made via fatty acid biosynthesis in the form of octanoyl-acyl carrier protein. In eukaryotes, a second fatty acid biosynthetic pathway in mitochondria is used for this purpose.[5][6] The octanoate is transferred from a thioester of acyl carrier protein to an amide of the lipoyl domain by an octanoyltransferase. The sulfur centers are inserted into the 6th and 8th carbons of octanoate via a radical SAM mechanism, by lipoyl synthase. The sulfurs are from the lipoyl synthase polypeptide.[7] As a result, lipoic acid is synthesized on the lipoyl domain and no free lipoic acid is produced. Lipoic acid can be removed whenever proteins are degraded and by action of the enzyme lipoamidase.[8] Free lipoate can be attached to the lipoyl domain by the enzyme lipoate protein ligase. The ligase activity of this enzyme requires ATP. Lipoate protein ligases proceed via an enzyme bound lipoyl adenylate intermediate.[9]
Lipoic acid-dependent complexes[edit]
2-OADH transfer reactions occur by a similar mechanism in the PDH complex, 2-oxoglutarate dehydrogenase (OGDH) complex, branched chain oxoacid dehydrogenase (BCDH) complex, and acetoin dehydrogenase (ADH) complex. The most studied of these is the PDH complex. These complexes have three central subunits: E1-3, which are the decarboxylase, lipoyl transferase, and dihydrolipoamide dehydrogenase respectively. These complexes have a central E2 core and the other subunits surround this core to form the complex. In the gap between these two subunits, the lipoyl domain ferries intermediates between the active sites.[10][11] The geometry of the PDH E2 core is cubic in Gram-negative bacteria or dodecahedral in Eukaryotes and Gram-positive bacteria. Interestingly the 2-OGDH and BCDH geometry is always cubic.[12] The lipoyl domain itself is attached by a flexible linker to the E2 core and the number of lipoyl domains varies from one to three for a given organism. The number of domains has been experimentally varied and seems to have little effect on growth until over nine are added, although more than three decreased activity of the complex.[13] The lipoyl domains within a given complex are homogenous, while at least two major clusters of lipoyl domains exist in sequenced organisms.[14]
Endogenous (enzyme-bound) (R)-lipoate also participates in transfer of acyl groups in the α-keto-glutarate dehydrogenase complex (KDHC or OGDC) and the branched-chain oxo acid dehydrogenase complex (BCOADC). RLA transfers a methylamine group in the glycine cleavage complex (GCV). RLA serves as co-factor to the acetoin dehydrogenase complex (ADC) catalyzing the conversion of acetoin (3-hydroxy-2-butanone) to acetaldehyde and acetyl coenzyme A, in some bacteria, allowing acetoin to be used as the sole carbon source.
The Glycine cleavage system differs from the other complexes, and has a different nomenclature. In this complex the H protein is a free lipoyl domain with additional helices, the L protein is a dihydrolipoamide dehydrogenase, the P protein is the decarboxylase, and the T protein transfers the methylamine from lipoate to tetrahydrofolate (THF) yielding methylene-THF and ammonia. Methylene-THF is then used by serine hydroxymethyltransferase (SHMT) to synthesize serine from glycine. This system is used by many organisms and plays a crucial role in the photosynthetic carbon cycle.[15]
Biological sources and degradation[edit]
Lipoic acid is present in almost all foods, but slightly more so in kidney, heart, liver, spinach, broccoli, and yeast extract.[16] Naturally occurring lipoic acid is always covalently bound and not readily available from dietary sources. Additionally, the amount of lipoic acid present in dietary sources is very low. For instance, the purification of lipoic acid to determine its structure used an estimated 10 tons of liver residue, which yielded 30 mg of lipoic acid.[17] As a result, all lipoic acid available as a supplement is chemically synthesized.
Baseline levels (prior to supplementation) of RLA and R-DHLA have not been detected in human plasma.[18] RLA has been detected at 12.3−43.1 ng/mL following acid hydrolysis, which releases protein-bound lipoic acid. Enzymatic hydrolysis of protein bound lipoic acid released 1.4−11.6 ng/mL and <1-38.2 ng/mL using subtilisin and alcalase, respectively.[19][20][21] It has not been determined whether pre-supplementation levels of RLA derive from food sources, mitochondrial turnover and salvaging or from gut microbes but low levels have been correlated to a variety of disease states.[22][23][24][25]
Digestive proteolytic enzymes cleave the R-lipoyllysine residue from the mitochondrial enzyme complexes derived from food but are unable to cleave the (R)-lipoic acid-L-lysine amide bond.[26] Both synthetic lipoamide and (R)-lipoyl-L-lysine are rapidly cleaved by serum lipoamidases which release free (R)-lipoic acid and either L-lysine or ammonia into the bloodstream.[24][27][27][28][29][30] It is questionable whether food sources of RLA provide any measurable benefit nutritionally or therapeutically due to the very low concentrations present.[31] Lipoate is the conjugate base of lipoic acid and as such is the most prevalent form under physiologic conditions. Most endogenous RLA is not "free" because octanaote is attached to the enzyme complexes that use it via LipA. The sulfur atoms derive from the amino acid L-cysteine and add asymmetrically to octanoate by lipoate synthase, thus generating the chiral center at C6.[32] Endogenous RLA has been found outside the mitochondria associated with the nucleus, peroxisomes and other organelles.[33][34] It has been suggested that the reduced form, R-DHLA may be the substrate for membrane-associated prostaglandin E-2 synthase (mPGES2).[35]
Pharmacology and medical uses of free lipoic acid[edit]
Today, R/S-LA and RLA are widely available as over-the-counter nutritional supplements in the United States in the form of capsules, tablets and aqueous liquids, and have been branded as antioxidants. This label has recently been challenged.[2] In Japan, LA is marketed primarily as a "weight loss" and "energy" supplement. The relationships between supplemental doses and therapeutic doses have not been clearly defined. Because lipoic acid is not an essential nutrient, no Recommended Daily Allowance (RDA) has been established. In Germany, LA is approved as a drug against diabetes comorbidities since 1966 and available by prescription.
According to the American Cancer Society, "there is no reliable scientific evidence at this time that lipoic acid prevents the development or spread of cancer".[36]
For use in dietary supplement materials and compounding pharmacies, the USP has established an official monograph for racemic R/S-LA.[37]
Possible beneficial effects[edit]
Lipoic acid has been the subject of numerous research studies and clinical trials:
- Prevent organ dysfunction[38]
- Treat or prevent cardiovascular disease[41]
- Accelerate chronic wound healing[42]
- Reduce iron overload[47]
- Prevent migraines[58]
- Treat chronic diseases associated with oxidative stress[62]
- Reduce inflammation[63]
- Treat peripheral artery disease.[65]
RLA is a classic example of an orthomolecular nutrient, in the original sense of Linus Pauling.
This section contains information of unclear or questionable importance or relevance to the article's subject matter. Please help improve this article by clarifying or removing superfluous information. |
Because of the low cost and ease of manufacturing R/S-LA relative to RLA, as well as early successes in treatments, the racemic form was more widely used nutritionally and clinically in Europe and Japan, despite the early recognition that the various forms of LA were not bioequivalent.[66] The original rationale for using (R/S)-lipoic acid as a nutritional supplement was that endogenous RLA was known to have biochemical properties like a B-vitamin (acting as a substrate or cofactor essential for enzyme function). It was also recognized that lower endogenous concentrations of RLA were found in tissues of humans with various diseases, and lower levels of RLA were found in the 24 hour urine of patients with various diseases than in healthy subjects.[23][24][25][67][68] Injections of R/S-LA as low as 10–25 mg normalized daily urinary output and, in many cases, improved patient health. When it was demonstrated that mammals have the genes to endogenously synthesize RLA, it lost vitamin status, but is today considered to be a "conditionally essential nutrient".[69] The exact mechanisms of how RLA levels decline with age and in various progressive diseases is unknown. In addition, microbial assays used to quantify LA were essentially stereospecific for RLA (100% active for RLA, 0% activity for SLA), so it was believed SLA was essentially inert or of very low biological activity. This was proven false by Gal, who demonstrated stereospecific toxicity of the (S)-enantiomer in thiamine-deficient rats.[70][71]
Several papers found RLA and acetyl carnitine reversed age-related markers in old rats to youthful levels.[72][73][74][75][76][77][78]
RLA may function in vivo like a B-vitamin and at higher doses like plant-derived nutrients, such as curcumin, sulphoraphane, resveratrol, and other nutritional substances that induce phase II detoxification enzymes, thus acting as cytoprotective agents.[79][80] This stress response indirectly improves the antioxidant capacity of the cell.[2]
A recent human pharmacokinetic study of RLA demonstrated the maximum concentration in plasma and bioavailability are significantly greater than the free acid form, and rivals plasma levels achieved by intravenous administration of the free acid form.[81] Additionally, high plasma levels comparable to those in animal models where Nrf2 was activated were achieved.[81]
Adverse effects[edit]
This section does not cite any references or sources. (September 2012) |
Side effects of alpha lipoic acid may include headache, tingling or a "pins and needles" sensation, skin rash, or muscle cramps. There have been a few reports in Japan of a rare condition called insulin autoimmune syndrome in people using alpha lipoic acid.[citation needed][82] The condition causes hypoglycemia and antibodies directed against the body's own insulin without previous insulin therapy. The safety of alpha lipoic acid in pregnant or nursing women, children, or people with kidney or liver disease is unknown. The toxic dose in cats is much lower than that in humans or dogs [83] and produces hepatocellular toxicity.
Antioxidant and prooxidant effects of lipoic acid[edit]
All of the disulfide forms of LA (R/S-LA, RLA and SLA) can be reduced to DHLA although both tissue specific and stereoselective (preference for one enantiomer over the other) reductions have been reported in model systems. At least two cytosolic enzymes, glutathione reductase (GR) and thioredoxin reductase (Trx1), and two mitochondrial enzymes, lipoamide dehydrogenase and thioredoxin reductase (Trx2), reduce LA. SLA is stereoselectively reduced by cytosolic GR whereas Trx1, Trx2 and lipoamide dehydrogenase stereoselectively reduce RLA. (R)-(+)-lipoic acid is enzymatically or chemically reduced to (R)-(-)-dihydrolipoic acid whereas (S)-(-)-lipoic acid is reduced to (S)-(+)-dihydrolipoic acid.[84][85][86][87][88][89][90] Dihydrolipoic acid (DHLA) can also form intracellularly and extracellularly via non-enzymatic, thiol-disulfide exchange reactions.[91]
The cytosolic and mitochondrial redox state is maintained in a reduced state relative to the extracellular matrix and plasma due to high concentrations of glutathione.[92][93] Despite the strongly reducing milieu, LA has been detected intracellularly in both oxidized and reduced forms.[94] Free LA is rapidly metabolized to a variety of shorter chain metabolites (via β-oxidation and either mono or bis-methylation) that have been identified and quantified intracellularly, in plasma and in urine.[95][96]
The antioxidant effects of LA were demonstrated when it was found to prevent the symptoms of vitamin C and vitamin E deficiency.[97] LA is reduced intracellularly to dihydrolipoic acid, which in cell culture regenerates by reduction of antioxidant radicals, such as vitamin C and vitamin E.[94] LA is able to scavenge reactive oxygen and reactive nitrogen species in vitro due to long incubation times, but there is little evidence this occurs in vivo or that radical scavenging contributes to the primary mechanisms of action of LA.[2][31] The relatively good scavenging activity of LA toward hypochlorous acid (a bactericidal produced by neutrophils that may produce inflammation and tissue damage) is due to the strained conformation of the 5-membered dithiolane ring, which is lost upon reduction to DHLA. In cells, LA is reduced to dihydrolipoic acid, which is generally regarded as the more bioactive form of LA and the form responsible for most of the antioxidant effects.[98] This theory has been challenged due to the high level of reactivity of the two free sulfhydryls, low intracellular concentrations of DHLA as well as the rapid methylation of one or both sulfhydryls, rapid side chain oxidation to shorter metabolites and rapid efflux from the cell. Although both DHLA and LA have been found inside cells after administration, most intracellular DHLA probably exists as mixed disulfides with various cysteine residues from cytosolic and mitochondrial proteins.[99] Recent findings suggest therapeutic and anti-aging effects are due to modulation of signal transduction and gene transcription, which improve the antioxidant status of the cell. Paradoxically, this likely occurs via pro-oxidant mechanisms, not by radical scavenging or reducing effects.[2][31][79]
Metal chelation[edit]
Owing to the presence of two thiol groups, dihydrolipoic acid is a chelating agent. It chelates both intracellular and extracellular mercury in the brain and in the body.[citation needed] Alpha Lipoic Acid (ALA) has a half life of 3 hours. Lipoic acid administration can significantly enhance biliary excretion of inorganic mercury in rat experiments, although it is not known if this is caused by chelation by lipoic acid or some other mechanism.[100] Lipoic acid has the potential to cross the blood–brain barrier in humans, unlike DMSA and DMPS; its effectiveness, however, is heavily dependent on the dosage and frequency of application.[101]
Medicinal differences between (R)-lipoic acid and (S)-lipoic acid[edit]
RLA is essential for life and aerobic metabolism, and RLA is the form biosynthesized in humans and other organisms studied so far. SLA is produced in equal amounts with RLA during achiral manufacturing processes. The racemic form was more widely used clinically in Europe and Japan in the 1950s to 1960s despite the early recognition that the various forms of LA were not bioequivalent.[66] The first synthetic procedures appeared for RLA and SLA in the mid 1950s.[102][103][104][105] Advances in chiral chemistry led to more efficient technologies for manufacturing the single enantiomers by both classical resolution and asymmetric synthesis and the demand for RLA also grew at this time. In the 21st century, R/S-LA, RLA and SLA with high chemical and/or optical purities are available in industrial quantities. Currently most of the world supply of R/S-LA and RLA is manufactured in China and smaller amounts in Italy, Germany and Japan. RLA is produced by modifications of a process first described by Georg Lang in a Ph.D. thesis and later patented by DeGussa.[106][107] Although RLA is favored nutritionally due to its "vitamin-like" role in metabolism, both RLA and R/S-LA are widely available as dietary supplements. Both stereospecific and non-stereospecific reactions are known to occur in vivo and contribute to the mechanisms of action but evidence to date indicates RLA may be the eutomer (the nutritionally and therapeutically preferred form).[99][108]
SLA is generally considered safe and nontoxic. It has been shown to be more toxic to thiamine deficient rats, but the mechanism or implications of this are not clear.[71] SLA did not exist prior to chemical synthesis in 1952.[109][110] The (S)-enantiomer (SLA) can assist in the reduction of the RLA when a racemic (50% (R)-enantiomer and 50% (S)-enantiomer) mixture is given.[111] Several studies have demonstrated that SLA either has lower activity than RLA or interferes with the specific effects of RLA by competitive inhibition.[112][113][114][115][116]
Lipoic acid in vivo seems primarily to induce the oxidative stress response rather than directly scavenge free radicals (see above). This effect is specific for RLA.[2] Very few studies compare individual enantiomers with racemic lipoic acid. It is unclear if twice as much racemic lipoic acid can replace RLA.[81]
Clinical trials and approved uses[edit]
RLA is being used in a federally funded clinical trial for multiple sclerosis at Oregon Health and Science University.[117] (R)-Lipoic acid is currently being used in two federally funded clinical trials at Oregon State University to test its effects in preventing heart disease and atherosclerosis.[118][119] Alpha-lipoic acid is approved in Germany as a drug for the treatment of polyneuropathies, such as diabetic and alcoholic polyneuropathies, and liver disease.
Intravenous Delivery[edit]
In the 1970's the first human clinical studies using alpha-lipoic acid (ALA) in the United States were carried out by Fredrick C. Bartter MD, Burton M. Berkson MD PhD, and associates from the National Institutes of Health. They administered intravenous ALA (racemic) to 79 people with acute and severe liver damage at various medical centers across the United States and 75 recovered full liver function Dr.'s Bartter and Berkson were subsequently appointed the FDA chief investigators for this therapeutic agent and Dr. Berkson went on to use it successfully for the treatment of chronic liver disease (viral hepatitis, autoimmune hepatitis, etc)
Because of ALA's ability to modify gene expression by stabilizing NF kappa B transcription, Berkson started using intravenous ALA for the treatment of various cancers for which no effective treatments exist. In a 2006 publication, he and co-authors described the long term survival of a patient with metastatic pancreatic cancer using ALA and various oral antioxidants<
- ^ Teichert J, Hermann R, Ruus P, Preiss R (November 2003). "Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers". J Clin Pharmacol 43 (11): 1257–67. doi:10.1177/0091270003258654. PMID 14551180.
- ^ a b c d e f Petersen Shay, K, Moreau, RF, Smith, EJ, Hagen, TM (June 2008). "Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity". IUBMB life 60 (6): 362–7. doi:10.1002/iub.40. PMID 18409172.
- ^ Reljanovic M, Reichel G, Rett K, et al. (September 1999). "Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy". Free Radic. Res. 31 (3): 171–9. PMID 10499773.
- ^ Raddatz, G, Bisswanger, H (October 1997). "Receptor site and stereospecifity of dihydrolipoamide dehydrogenase for R- and S-lipoamide: a molecular modeling study". Journal of Biotechnology 58 (2): 89–100. doi:10.1016/S0168-1656(97)00135-1. PMID 9383983.
- ^ Cronan JE, Fearnley IM, Walker JE. (2005). "Mammalian mitochondria contain a soluble acyl carrier protein". FEBS Lett. 579 (21): 4892–6. doi:10.1016/j.febslet.2005.07.077. PMID 16109413.
- ^ Jordan SW, Cronan JE Jr. (1997). "A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria". J. Biol. Chem. 272 (29): 17903–6. doi:10.1074/jbc.272.29.17903. PMID 9218413.
- ^ Cicchillo RM, Booker SJ. (2005). "Mechanistic investigations of lipoic acid biosynthesis in E. coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide". J. Am. Chem. Soc. 127 (9): 2860–1. doi:10.1021/ja042428u. PMID 15740115.
- ^ Jiang Y, Cronan JE. (2005). "Expression cloning and demonstration of Enterococcus faecalis lipoamidase (pyruvate dehydrogenase inactivase) as a Ser-Ser-Lys triad amidohydrolase". J. Biol. Chem. 280 (3): 2244–56. doi:10.1074/jbc.+M408612200. PMID 15528186.
- ^ Cronan JE, Zhao X, Jiang Y. (2005). "Function, attachment and synthesis of lipoic acid in Escherichia coli". Adv. Microb. Physiol. 50: 103–46. doi:10.1016/S0065-2911(05)50003-1. PMID 16221579.
- ^ Milne JL, Wu X, Borgnia MJ, Lengyel JS, Brooks BR, Shi D, Perham RN, Subramaniam S. (2006). "Molecular Structure of a 9-MDa Icosahedral Pyruvate Dehydrogenase Subcomplex Containing the E2 and E3 Enzymes Using Cryoelectron Microscopy". J. Biol. Chem. 281 (7): 4364–4370. doi:10.1074/jbc.+M504363200. PMC 1647297. PMID 16308322. [1]
- ^ Murphy GE, Jensen GJ. (2005). "Electron cryotomography of the E. coli pyruvate and 2-oxoglutarate dehydrogenase complexes". Structure 13 (12): 1765–1773. doi:10.1016/j.str.2005.08.016. PMID 16338405. [2]
- ^ Izard T, Aevarsson A, Allen MD, Westphal AH, Perham RN, de Kok A, Hol WG. (1999). "Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes". Proc. Natl. Acad. Sci. USA 96 (4): 1240–1245. doi:10.1073/pnas.96.4.1240. PMC 15447. PMID 9990008. [3]
- ^ Machado RS, Clark DP, and Guest JR (1992). "Construction and properties of pyruvate dehydrogenase complexes with up to nine lipoyl domains per lipoate acetyltransferase chain". FEMS Microbiol. Lett. 79 (1–3): 243–248. doi:10.1111/j.1574-6968.1992.tb05710.x. PMID 1478460.
- ^ Omelchenko MV, Makarova KS, and Koonin EV (2002). "Recurrent intragenomic recombination leading to sequence homogenization during the evolution of the lipoyl-binding domain". J. FEMS Microbiol. Lett. 209 (2): 255–260. doi:10.1111/j.1574-6968.2002.tb11140.x.
- ^ Douce R, Bourguignon J, Neuburger M, and Rebeille F (2001). "The glycine decarboxylase system: a fascinating complex". Trends Plant Sci. 6 (4): 167–176. doi:10.1016/S1360-1385(01)01892-1. PMID 11286922.
- ^ Durrani, Arjumand I. Schwartz H, Nagl M, Sontag G. (Oct 2010). "Determination of free [alpha]-lipoic acid in foodstuffs by HPLC coupled with CEAD and ESI-MS". Food Chemistry 120 (4): 38329–36. doi:10.1016/j.foodchem.2009.11.045.
- ^ Reed LJ (Oct 2001). "A Trail of Research from Lipoic Acid to alpha-Keto Acid Dehydrogenase Complexes". J. Biol. Chem. 276 (42): 38329–36. doi:10.1074/jbc.+R100026200. PMID 11477096.
- ^ Hermann R, Niebch G, Borbe HO, Fieger H, Ruus P, Nowak H, Riethmuller-Winzen H, Peukert M, Blume H. (1996). "Enantioselective pharmacokinetics and bioavailability of different racemic formulations in healthy volunteers". Eur J Pharm Sci 4 (3): 167–174. doi:10.1016/0928-0987(95)00045-3.
- ^ Teichert, J, Preiss, R (1997). "High-performance liquid chromatography methods for determination of lipoic and dihydrolipoic acid in human plasma". Methods in Enzymology. Methods in Enzymology 279: 159–66. doi:10.1016/S0076-6879(97)79019-0. ISBN 978-0-12-182180-7. PMID 9211267.
- ^ Teichert, J, Preiss, R (October 1995). "Determination of lipoic acid in human plasma by high-performance liquid chromatography with electrochemical detection". Journal of Chromatography B 672 (2): 277–81. doi:10.1016/0378-4347(95)00225-8. PMID 8581134.
- ^ Teichert, J, Preiss, R (November 1992). "HPLC-methods for determination of lipoic acid and its reduced form in human plasma". International Journal of Clinical Pharmacology, Therapy, and Toxicology 30 (11): 511–2. PMID 1490813.
- ^ Baker, H, Deangelis, B, Baker, ER, Hutner, SH (September 1998). "A practical assay of lipoate in biologic fluids and liver in health and disease". Free Radical Biology & Medicine 25 (4–5): 473–9. doi:10.1016/S0891-5849(98)00087-2. PMID 9741583.
- ^ a b Takenouchi, K, Aso, K, Kawashima, S (June 1962). "Studies on the metabolism of thioctic acid in skin diseases. II. Loading test of thioctic acid in various skin diseases". Journal of Vitaminology 8: 99–114. PMID 13984665.
- ^ a b c Wada, M, Shigeta, Y, Inamori, K (September 1961). "A study on the metabolism of lipoic acid and lipoamide". Journal of Vitaminology 7: 237–42. PMID 14004240.
- ^ a b Shigeta Y, Hiraizumi G, Wada M, Oji K, Yoshida T. Study on the Serum Level of Thioctic Acid in Patients with Various Diseases. J Vitaminology. (1961) 7:48-52
- ^ Biewenga, GP, Haenen, GR, Bast, A (September 1997). "The pharmacology of the antioxidant lipoic acid". General Pharmacology 29 (3): 315–31. doi:10.1016/S0306-3623(96)00474-0. PMID 9378235.
- ^ a b Oizumi, J, Hayakawa, K (July 1989). "Liberation of lipoate by human serum lipoamidase from bovine heart pyruvate dehydrogenase". Biochemical and Biophysical Research Communications 162 (2): 658–63. doi:10.1016/0006-291X(89)92361-9. PMID 2502979.
- ^ Saito J (1960). "The Conversion of Thioctamide to Thioctic acid in Biological Systems. I. The thioctic Active Substances in Rabbit Serum after Administration of Thioctamide". Vitamin 21 (3): 359–63.
- ^ Backman-Gullers, B, Hannestad, U, Nilsson, L, Sorbo, B (October 1990). "Studies on lipoamidase: characterization of the enzyme in human serum and breast milk". Clinica Chimica Acta 191 (1–2): 49–60. doi:10.1016/0009-8981(90)90057-Y. PMID 2127386.
- ^ Garganta, CL, Wolf, B (August 1990). "Lipoamidase activity in human serum is due to biotinidase". Clinica Chimica Acta 189 (3): 313–25. doi:10.1016/0009-8981(90)90313-H. PMID 2225462.
- ^ a b c Shay, KP, Moreau, RF, Smith, EJ, Smith, AR, Hagen, TM (October 2009). "Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential". Biochimica et Biophysica Acta 1790 (10): 1149–60. doi:10.1016/j.bbagen.2009.07.026. PMC 2756298. PMID 19664690.
- ^ Packer & Patel 2008, Nesbitt NM, Cicchillo RM, Lee KH, Grove TL, Booker SJ. Ch. 2 "Lipoic Acid Biosynthesis"
- ^ Mascitelli-Coriandoli, E, Citterio, C (November 1959). "Intracellular thioctic acid and coenzyme A following vanadium treatment". Nature 184 (4699): 1641. doi:10.1038/1841641a0. PMID 14421987.
- ^ Marchesini, S, Poirier, Y (August 2003). "Futile cycling of intermediates of fatty acid biosynthesis toward peroxisomal beta-oxidation in Saccharomyces cerevisiae". Journal of Biological Chemistry 278 (35): 32596–601. doi:10.1074/jbc.M305574200. PMID 12819196.
- ^ Watanabe, K, Ohkubo, H, Niwa, H, Tanikawa, N, Koda, N, Ito, S, Ohmiya, Y (June 2003). "Essential 110Cys in active site of membrane-associated prostaglandin E synthase-2". Biochemical and Biophysical Research Communications 306 (2): 577–81. doi:10.1016/S0006-291X(03)01025-8. PMID 12804604.
- ^ "Lipoic Acid". American Cancer Society. November 2008. Retrieved 5 October 2013.
- ^ Alpha Lipoic Acid C8H14O2S2 206.33
- ^ Gianturco, V, Bellomo, A, D'ottavio, E, Formosa, V, Iori, A, Mancinella, M, Troisi, G, Marigliano, V (2009). "Impact of therapy with alpha-lipoic acid (ALA) on the oxidative stress in the controlled NIDDM: a possible preventive way against the organ dysfunction?". Archives of gerontology and geriatrics 49 (Suppl 1): 129–33. doi:10.1016/j.archger.2009.09.022. PMID 19836626.
- ^ Morcos, M, Borcea, V, Isermann, B, Gehrke, S, Ehret, T, Henkels, M, Schiekofer, S, Hofmann, M et al. (June 2001). "Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study". Diabetes research and clinical practice 52 (3): 175–83. doi:10.1016/S0168-8227(01)00223-6. PMID 11323087.
- ^ Vossler, S, Füllert, S, Schneider, F, Haak, E, Haak, T, Samigullin, R, Tritschler, H, Tooke, JE et al. (July 2007). "Pharmacodynamic effects of orally administered dexlipotam on endothelial function in type 2-diabetic patients". International journal of clinical pharmacology and therapeutics 45 (7): 385–93. PMID 17725245.
- ^ Ghibu, S, Richard, C, Vergely, C, Zeller, M, Cottin, Y, Rochette, L (November 2009). "Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases". Journal of cardiovascular pharmacology 54 (5): 391–8. doi:10.1097/FJC.0b013e3181be7554. PMID 19998523.
- ^ Alleva, R, Nasole, E, Di Donato, F, Borghi, B, Neuzil, J, Tomasetti, M (July 2005). "alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy". Biochemical and Biophysical Research Communications 333 (2): 404–10. doi:10.1016/j.bbrc.2005.05.119. PMID 15950945.
- ^ Chang, JW, Lee, EK, Kim, TH, Min, WK, Chun, S, Lee, KU, Kim, SB, Park, JS (2007). "Effects of alpha-lipoic acid on the plasma levels of asymmetric dimethylarginine in diabetic end-stage renal disease patients on hemodialysis: a pilot study". American journal of nephrology 27 (1): 70–4. doi:10.1159/000099035. PMID 17259696.
- ^ Femiano, F, Scully, C, Gombos, F (December 2002). "Idiopathic dysgeusia; an open trial of alpha lipoic acid (ALA) therapy". International journal of oral and maxillofacial surgery 31 (6): 625–8. doi:10.1054/ijom.2002.0276. PMID 12521319.
- ^ Femiano, F, Scully, C (May 2002). "Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy". Journal of Oral Pathology & Medicine 31 (5): 267–9. doi:10.1034/j.1600-0714.2002.310503.x. PMID 12110042.
- ^ Patton, LL, Siegel, MA, Benoliel, R, De Laat, A (March 2007). "Management of burning mouth syndrome: systematic review and management recommendations". Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 103 (Suppl): S39.e1–13. doi:10.1016/j.tripleo.2006.11.009. PMID 17379153.
- ^ Kundiev, IuI, Lubianova, IP, Mikhaĭlik, OM, Dudchenko, NO, Lampeka, EG (2001). "Berlition R 300 oral -- alpha-lipoic acid preparation for the correction of body changes associated with high serum iron content". Meditsina truda i promyshlennaia ekologiia (1): 14–8. PMID 11221104.
- ^ Sola, S, Mir, MQ, Cheema, FA, Khan-Merchant, N, Menon, RG, Parthasarathy, S, Khan, BV (January 2005). "Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study". Circulation 111 (3): 343–8. doi:10.1161/01.CIR.0000153272.48711.B9. PMID 15655130.
- ^ Minokoshi, Y, Alquier, T, Furukawa, N, Kim, YB, Lee, A, Xue, B, Mu, J, Foufelle, F et al. (April 2004). "AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus". Nature 428 (6982): 569–74. doi:10.1038/nature02440. PMID 15058305.
- ^ Ying, Z, Kherada, N, Farrar, B, Kampfrath, T, Chung, Y, Simonetti, O, Deiuliis, J, Desikan, R et al. (January 2010). "Lipoic acid effects on established atherosclerosis". Life Sciences 86 (3–4): 95–102. doi:10.1016/j.lfs.2009.11.009. PMC 3075920. PMID 19944706.
- ^ Liu, J (January 2008). "The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview". Neurochemical research 33 (1): 194–203. doi:10.1007/s11064-007-9403-0. PMID 17605107.
- ^ Packer, L, Tritschler, HJ, Wessel, K (1997). "Neuroprotection by the metabolic antioxidant alpha-lipoic acid". Free radical biology & medicine 22 (1–2): 359–78. doi:10.1016/S0891-5849(96)00269-9. PMID 8958163.
- ^ Holmquist, L, Stuchbury, G, Berbaum, K, Muscat, S, Young, S, Hager, K, Engel, J, Münch, G (January 2007). "Lipoic acid as a novel treatment for Alzheimer's disease and related dementias". Pharmacology & therapeutics 113 (1): 154–64. doi:10.1016/j.pharmthera.2006.07.001. PMID 16989905.
- ^ Hager, K, Kenklies, M, McAfoose, J, Engel, J, Münch, G (2007). "Alpha-lipoic acid as a new treatment option for Alzheimer's disease—a 48 months follow-up analysis". Journal of neural transmission. Supplementum (72): 189–93. PMID 17982894.
- ^ MacZurek, A, Hager, K, Kenklies, M, Sharman, M, Martins, R, Engel, J, Carlson, DA, Münch, G (2008). "Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease". Advanced drug delivery reviews 60 (13–14): 1463–70. doi:10.1016/j.addr.2008.04.015. PMID 18655815.
- ^ Hurdag, C, Ozkara, H, Citci, S, Uyaner, I, Demirci, C (2005). "The effects of alpha-lipoic acid on nitric oxide synthetase dispersion in penile function in streptozotocin-induced diabetic rats". International journal of tissue reactions 27 (3): 145–50. PMID 16372481.
- ^ Yao, LS, Wang, YT, Chen, Y, Dai, YT (October 2009). "Expressions of NOS isoforms in the cavernous tissues of diabetic rat models". Zhonghua nan ke xue = National journal of andrology 15 (10): 915–9. PMID 20112741.
- ^ Magis, D, Ambrosini, A, Sándor, P, Jacquy, J, Laloux, P, Schoenen, J (January 2007). "A randomized double-blind placebo-controlled trial of thioctic acid in migraine prophylaxis". Headache 47 (1): 52–7. doi:10.1111/j.1526-4610.2006.00626.x. PMID 17355494.
- ^ Yadav, V, Marracci, G, Lovera, J, Woodward, W, Bogardus, K, Marquardt, W, Shinto, L, Morris, C et al. (April 2005). "Lipoic acid in multiple sclerosis: a pilot study". Multiple sclerosis (Houndmills, Basingstoke, England) 11 (2): 159–65. doi:10.1191/1352458505ms1143oa. PMID 15794388.
- ^ Salinthone, S, Yadav, V, Bourdette, DN, Carr, DW (June 2008). "Lipoic acid: a novel therapeutic approach for multiple sclerosis and other chronic inflammatory diseases of the CNS". Endocrine, metabolic & immune disorders drug targets 8 (2): 132–42. doi:10.2174/187153008784534303. PMID 18537699.
- ^ Yadav, V, Marracci, GH, Munar, MY, Cherala, G, Stuber, LE, Alvarez, L, Shinto, L, Koop, DR et al. (April 2010). "Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters". Multiple sclerosis (Houndmills, Basingstoke, England) 16 (4): 387–97. doi:10.1177/1352458509359722. PMID 20150394.
- ^ Smith, AR, Shenvi, SV, Widlansky, M, Suh, JH, Hagen, TM (May 2004). "Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress". Current medicinal chemistry 11 (9): 1135–46. PMID 15134511.
- ^ Zhang WJ, Wei H, Hagen T, Frei B (2007). "α-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway". Proc Natl Acad Sci U S A. 104 (10): 4077–82. doi:10.1073/pnas.0700305104. PMC 1805485. PMID 17360480.
- ^ Vasdev, S, Gill, V, Singal, P (2007). "Role of advanced glycation end products in hypertension and atherosclerosis: therapeutic implications". Cell biochemistry and biophysics 49 (1): 48–63. doi:10.1007/s12013-007-0039-0. PMID 17873339.
- ^ Vincent, HK, Bourguignon, CM, Vincent, KR, Taylor, AG (June 2007). "Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study". Journal of alternative and complementary medicine 13 (5): 577–84. doi:10.1089/acm.2007.6177. PMID 17604563.
- ^ a b Kleeman A, Borbe HO, Ulrich H. Thioctic Acid-Lipoic Acid; in Thioctic Acid. New Biochemistry, Pharmacology and Findings from Clinical Practice with Thioctic Acid. 11-26. Borbe; Ulrich (Hrsg.) Verfasser: Reschke, Barbara ; Borbe, Harald [Hrsg.]Verleger: [Frankfurt (Main)] : pmi (1991)
- ^ Hiraizumi G (1959). "Alpha Lipoic Acid Metabolism in Various Diseases. II. The Urinary Excretion and Serum level of Alpha Lipoic Acid in Patients with Various Diseases". Bitamin 18 (1): 184–8.
- ^ Wada M, Hiraizumi G, Shigeta Y (1960). "The Urinary Excretion and Serum Level of a-lipoic acid in Patients with Several Diseases". Maikurobaioassei (Microbioassay) 1: 53–5.
- ^ http://www.direct-ms.org/pdf/NutritionNonAuto/Ames%20Delaying%20Aging%20with%20ALCAR.pdf
- ^ Gal, EM, Razevska, DE (August 1960). "Studies on the in vivo metabolism of lipoic acid. 1. The fate of DL-lipoic acid-S35 in normal and thiamine-deficient rats". Archives of biochemistry and biophysics 89 (2): 253–61. doi:10.1016/0003-9861(60)90051-5. PMID 13825981.
- ^ a b Gal, EM (July 1965). "Reversal of selective toxicity of (-)-alpha-lipoic acid by thiamine in thiamine-deficient rats". Nature 207 (996): 535. doi:10.1038/207535a0. PMID 5328673.
- ^ Lecoq, R, Chauchard, P, Mazoue, H (October 1958). "Comparative chronaxymetric research on the effects of several vitaminic substances (stigmasterol, carnitine, thioctic acid)". Comptes rendus hebdomadaires des séances de l'Académie des sciences 247 (17): 1411–3. PMID 13609011.
- ^ McCarty, MF (April 1981). "Toward a "bio-energy supplement" -- a prototype for functional orthomolecular supplementation". Medical hypotheses 7 (4): 515–38. doi:10.1016/0306-9877(81)90038-4. PMID 6793816.
- ^ Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN (Sep 1998). "Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes--reversal with (R)-alpha-lipoic acid supplementation". FASEB J. 12 (12): 1183–9. PMID 9737721.
- ^ Hagen, TM, Ingersoll, RT, Lykkesfeldt, J, Liu, J, Wehr, CM, Vinarsky, V, Bartholomew, JC, Ames, AB (February 1999). "(R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate". The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 (2): 411–8. PMID 9973329.
- ^ Hagen, TM, Vinarsky, V, Wehr, CM, Ames, BN (2000). "(R)-alpha-lipoic acid reverses the age-associated increase in susceptibility of hepatocytes to tert-butylhydroperoxide both in vitro and in vivo". Antioxidants & redox signaling 2 (3): 473–83. doi:10.1089/15230860050192251. PMID 11229361.
- ^ Hagen, TM, Liu, J, Lykkesfeldt, J, Wehr, CM, Ingersoll, RT, Vinarsky, V, Bartholomew, JC, Ames, BN (February 2002). "Feeding acetyl-l-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress". Proceedings of the National Academy of Sciences of the United States of America 99 (4): 1870–5. doi:10.1073/pnas.261708898. PMC 122286. PMID 11854487.
- ^ Liu, J; Head, E; Gharib, AM; Yuan, W; Ingersoll, RT; Hagen, TM; Cotman, CW; Ames, BN (2002). "Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-l-carnitine and/or R-α-lipoic acid". Proceedings of the National Academy of Sciences of the United States of America 99 (4): 2356–61. doi:10.1073/pnas.261709299. PMC 122369. PMID 11854529. Erratum in: Proc Natl Acad Sci U S A 2002 May 14;99(10):7184-5
- ^ a b Packer & Patel 2008, Petersen-Shay K, Shenvi S, Hagen TM. Ch. 14 "Lipoic acid as an inducer of phase II detoxification enzymes through activation of Nr-f2 dependent gene expression." pp. 349–371
- ^ Lii CK, Liu KL, Cheng YP, Lin AH, Chen HW, Tsai CW (May 2010). "Sulforaphane and alpha-lipoic acid upregulate the expression of the pi class of glutathione S-transferase through c-jun and Nrf2 activation". J. Nutr. 140 (5): 885–92. doi:10.3945/jn.110.121418. PMID 20237067.
- ^ a b c Carlson, DA, Smith, AR, Fischer, SJ, Young, KL, Packer, L (December 2007). "The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)-lipoate to healthy human subjects". Alternative medicine review : a journal of clinical therapeutic 12 (4): 343–51. PMID 18069903.
- ^ http://care.diabetesjournals.org/content/30/9/2240.full
- ^ Hill AS et al. (Apr 2004). J Anim Physiol Anim Nutr (Berl.) 88 (3-4): 150–6.
- ^ Arnér, ES, Nordberg, J, Holmgren, A (August 1996). "Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase". Biochemical and Biophysical Research Communications 225 (1): 268–74. doi:10.1006/bbrc.1996.1165. PMID 8769129.
- ^ Biaglow, JE, Ayene, IS, Koch, CJ, Donahue, J, Stamato, TD, Mieyal, JJ, Tuttle, SW (April 2003). "Radiation response of cells during altered protein thiol redox". Radiation research 159 (4): 484–94. doi:10.1667/0033-7587(2003)159[0484:RROCDA]2.0.CO;2. PMID 12643793.
- ^ Haramaki, N, Han, D, Handelman, GJ, Tritschler, HJ, Packer, L (1997). "Cytosolic and mitochondrial systems for NADH- and NADPH-dependent reduction of alpha-lipoic acid". Free radical biology & medicine 22 (3): 535–42. doi:10.1016/S0891-5849(96)00400-5. PMID 8981046.
- ^ Constantinescu, A, Pick, U, Handelman, GJ, Haramaki, N, Han, D, Podda, M, Tritschler, HJ, Packer, L (July 1995). "Reduction and transport of lipoic acid by human erythrocytes". Biochemical pharmacology 50 (2): 253–61. doi:10.1016/0006-2952(95)00084-D. PMID 7632170.
- ^ May, JM, Qu, ZC, Nelson, DJ (June 2006). "Cellular disulfide-reducing capacity: an integrated measure of cell redox capacity". Biochemical and Biophysical Research Communications 344 (4): 1352–9. doi:10.1016/j.bbrc.2006.04.065. PMID 16650819.
- ^ Jones, W, Li, X, Qu, ZC, Perriott, L, Whitesell, RR, May, JM (July 2002). "Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells". Free radical biology & medicine 33 (1): 83–93. doi:10.1016/S0891-5849(02)00862-6. PMID 12086686.
- ^ Schempp H, Ulrich H, Elstner EF (1994). "Stereospecific reduction of R(+)-thioctic acid by porcine heart lipoamide dehydrogenase/diaphorase". Z. Naturforsch., C, J. Biosci. 49 (9-10): 691–2. PMID 7945680.
- ^ Biewenga G Ph, Haenen GRMM, Bast A (1997). "Ch. 1 "An overview of Lipoate Chemistry"". In Fuchs J, Packer L, Zimmer G. Lipoic Acid In Health & Disease. Marcel Dekker. pp. 1–32.
- ^ Sen CK (1997). "Nutritional Biochemistry of Cellular Glutathione". Nutritional Biochemistry 8 (12): 660–672. doi:10.1016/S0955-2863(97)00113-7.
- ^ Marí, M, Morales, A, Colell, A, García-Ruiz, C, Fernández-Checa, JC (November 2009). "Mitochondrial Glutathione, a Key Survival Antioxidant". Antioxidants & redox signaling 11 (11): 2685–700. doi:10.1089/ARS.2009.2695. PMC 2821140. PMID 19558212.
- ^ a b Packer, L, Witt, EH, Tritschler, HJ (August 1995). "alpha-Lipoic acid as a biological antioxidant". Free radical biology & medicine 19 (2): 227–50. doi:10.1016/0891-5849(95)00017-R. PMID 7649494.
- ^ Harrison, EH, McCormick, DB (February 1974). "The metabolism of dl-(1,6-14C)lipoic acid in the rat". Archives of biochemistry and biophysics 160 (2): 514–22. doi:10.1016/0003-9861(74)90428-7. PMID 4598618.
- ^ Schupke, H, Hempel, R, Peter, G, Hermann, R, Wessel, K, Engel, J, Kronbach, T (June 2001). "New metabolic pathways of alpha-lipoic acid". Drug metabolism and disposition: the biological fate of chemicals 29 (6): 855–62. PMID 11353754.
- ^ Rosenberg, H (1959). "Effect of ?-lipoic acid on vitamin C and vitamin E deficiencies". Archives of Biochemistry and Biophysics 80: 86–93. doi:10.1016/0003-9861(59)90345-5.
- ^ Haenen, GRMM, Bast, A (1991). "Scavenging of hypochlorous acid by lipoic acid". Biochem Pharmacol 42 (11): 2244–6. doi:10.1016/0006-2952(91)90363-A. PMID 1659823.
- ^ a b Packer & Patel 2008, Carlson DA, Young KL, Fischer SJ, Ulrich H. Ch. 10 "An Evaluation of the Stability and Pharmacokinetics of R-lipoic Acid and R-Dihydrolipoic Acid Dosage Forms in Plasma from Healthy Human Subjects." pp. 235–270
- ^ Gregus, Z.; Stein, A.F, Varga, F., Klaassen, C.D. (1992). "Effect of lipoic acid on biliary excretion of glutathione and metals". Toxicology and Applied Pharmacology 114 (1): 88–96. doi:10.1016/0041-008X(92)90100-7. PMID 1585376.
- ^ Rooney, James, (2007). "The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury". Toxicology 234 (3): 145–156. doi:10.1016/j.tox.2007.02.016. PMID 17408840.
- ^ Fontanella, L (1955). "Preparation of optical antipodes of alpha-lipoic acid". Il Farmaco; edizione scientifica 10 (12): 1043–5. PMID 13294188.
- ^ Walton E, Wagner AF, Bachelor FW, Peterson LH, Holly FW, Folkers K (1955). "Synthesis of (+)-Lipoic Acid and its Optical Antipode". J. Am. Chem. Soc. 77 (19): 5144–9. doi:10.1021/ja01624a057.
- ^ Acker DS, Wayne WJ. (1957). "Optically Active and Radioactive α-Lipoic Acids". J. Am. Chem. Soc. 79: 6483. doi:10.1021/ja01581a033.
- ^ Deguchi, Y, Miura, K (June 1964). "Studies on the Synthesis of Thioctic acid and its related compounds. XIV. Synthesis of (+)-Thioctamide". Yakugaku Zasshi 84: 562–3. PMID 14207116.
- ^ Lang G. In Vitro Metabolism of a-Lipoic Acid Especially Taking Enantioselective Bio-transformation into Account. Ph.D. Thesis, University of Münster, Münster,Germany (1992)
- ^ Blaschke et al. Preparation and use of salts of the pure enantiomers of alpha-lipoic acid. US 5281722 (Jan 25, 1994)
- ^ Packer, L, Kraemer, K, Rimbach, G (October 2001). "Molecular aspects of lipoic acid in the prevention of diabetes complications". Nutrition (Burbank, Los Angeles County, Calif.) 17 (10): 888–95. doi:10.1016/S0899-9007(01)00658-X. PMID 11684397.
- ^ Hornberger CS, Heitmiller RF, Gunsalus IC, Schnakenberg GHF, Reed LJ (1953). "Synthesis of DL—Lipoic Acid". J. Am. Chem. Soc. 75 (6): 1273–7. doi:10.1021/ja01102a003.
- ^ Hornberger CS, Heitmiller RF, Gunsalus IC, Schnakenberg GHF, Reed LJ (1952). "Synthetic Preparation of Lipoic Acid". J. Am. Chem. Soc. 74 (9): 2382. doi:10.1021/ja01129a511.
- ^ Biewenga GP, Haenen GRMM, Groen BH, Biewenga JE, Van Grondelle R, Bast A (1997). "Combined non-enzymatic and enzymatic reduction favors bioactivation of racemic lipoic acid: an advantage of a racemic drug?". Chirality 9: 362–6.
- ^ Ulrich H, Weischer CH, Engel J, Hettche H. Pharmaceutical compositions containing R-alpha-lipoic acid or S-alpha.-lipoic acid as active ingredient. US 6,271,254 2001
- ^ Kilic, F, Handelman, GJ, Serbinova, E, Packer, L, Trevithick, JR (October 1995). "Modelling cortical cataractogenesis 17: in vitro effect of a-lipoic acid on glucose-induced lens membrane damage, a model of diabetic cataractogenesis". Biochemistry and molecular biology international 37 (2): 361–70. PMID 8673020.
- ^ Artwohl M, Schmetterer L, Rainer G, et al. Modulation by antioxidants of endothelial apoptosis, proliferation, & associated gene/protein expression. European Association for the Study of Diabetes. Program 36. Jerusalem, Israel; 2000: Abs 274
- ^ Streeper, RS, Henriksen, EJ, Jacob, S, Hokama, JY, Fogt, DL, Tritschler, HJ (July 1997). "Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle". The American journal of physiology 273 (1 Pt 1): E185–91. PMID 9252495.
- ^ Frölich, L, Götz, ME, Weinmüller, M, Youdim, MB, Barth, N, Dirr, A, Gsell, W, Jellinger, K et al. (March 2004). "(r)-, but not (s)-alpha lipoic acid stimulates deficient brain pyruvate dehydrogenase complex in vascular dementia, but not in Alzheimer dementia". Journal of neural transmission (Vienna, Austria : 1996) 111 (3): 295–310. doi:10.1007/s00702-003-0043-5. PMID 14991456.
- ^ ClinicalTrials.gov NCT00676156 A Study of the Pharmacokinetics and Immunologic Effects of Lipoic Acid in Multiple Sclerosis
- ^ ClinicalTrials.gov NCT00765310 Lipoic Acid and Prevention of Heart Disease
- ^ ClinicalTrials.gov NCT00764270 The Role of R-Alpha Lipoic Acid in the Treatment of Atherosclerotic Vascular Disease
Bartter F.C.; Berkson, B. M. G., J.; and Hiranaka, P. (1980) Treatment of Four Delayed-Mushroom-Poisoning Patients with Thioctic Acid., Baden-Baden, Koln, New York. Berkson, B. M. (1979) Thioctic acid in treatment of hepatotoxic mushroom (Phalloides) poisoning. N Engl J Med 300, 371. Berkson, B. M. (1980) Thioctic Acid in the Treatment of Poisoning with Alpha Amanitin, Baden-Baden, Koln, New York. Berkson, B. M. (1998) Alpha-Lipoic Acid (Thioctic Acid): My Experience with this Outstanding Therapeutic Agent. Journal of Orthomolecular Medicine 13, 44-48. Berkson, B. M. (1999) A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Med Klin (Munich) 94 Suppl 3, 84-9. Berkson, B. M. (2000) A Triple Antioxidant Approach to the Treatment of Hepatitis C Using Alpha-Lipoic Acid (Thioctic Acid), Silymarin, Selenium, and other Fundamental Nutraceuticals. Clinical Practice of Alternative Medicine 1, 27-33.</ref>.
Berkson, B. M., Rubin, D. M., and Berkson, A. J. (2006) The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low-dose naltrexone protocol. Integr Cancer Ther 5, 83-9.</ref>.
Berkson BM, Rubin DM, Berkson AJ. Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone. Integr Cancer Ther. 2007 Sep;6(3):293-6. Berkson BM, Rubin DM, Berkson AJ. Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases. Integr Cancer Ther. 2009 Dec;8(4):416-22. doi: 10.1177/1534735409352082. Erratum in: Integr Cancer Ther. 2010 Jun;9(2):247.
Other reviews[edit]
Wikimedia Commons has media related to lipoic acid. |
- Jane Higdon, "Lipoic Acid", Micronutrient Information Center, Linus Pauling Institute, Oregon State University
- Packer, Lester; Patel, Mulchand S., eds. (2008). Lipoic acid: energy production, antioxidant activity and health effects. Boca Raton: CRC Press. ISBN 1-4200-4537-7.


text:
"With a Kite - The Evolution of True Boarding" |
Wednesday, 11 April 2012 09:10 |
Last Updated on Wednesday, 11 April 2012 09:19 |
"With a Kite - The Evolution of True Boarding" |
Wednesday, 11 April 2012 09:10 |
Last Updated on Wednesday, 11 April 2012 09:19 |
Kelly Slater may retire from the ASP World Tour after Pipeline 09/12/2013
Kelly Slater, the best competitive surfer of all time, admits he may quit the ASP World Tour if he doesn't win the contest and the 2013 world title.
Perfect barrels open the 2013 Billabong Pipe Masters 09/12/2013
Firing six-to-eight foot (2 metre) waves opened the 2013 Billabong Pipe Masters In Memory of Andy Irons, at Banzai Pipeline, Hawaii.
+ Surfing News |
HTC Atlantic Kite Challenge celebrates halfway mark 09/12/2013
The HTC Atlantic Kite Challenge keeps adding miles to the Atlantic Ocean crossing.
Paraplegic woman goes kiteboarding 09/12/2013
A paraplegic woman has decided to try kiteboarding with special gear.
+ Kitesurfing News |
Vincent Langer returns to the Point-7 windsurfing team 09/12/2013
Vincent Langer has joined the Point-7 windsurfing team.
Chinese windsurfers blast the ISAF Sailing World Cup Melbourne 09/12/2013
China's Chuakun Shi sailed a near perfect week in the Men's RS:X, at ISAF Sailing World Cup Melbourne, to take a deserved gold medal.
+ Windsurfing News |
Big wave bodyboarders ready for action in Nazaré 09/12/2013
The 2014 Sumol Nazaré Special Edition will hit Praia do Norte, Portugal, between January 3rd-30th.
How to improve your bodyboarding 06/12/2013
Improve your bodyboarding skills with a collection of techniques, tips and advice given by a professional bodyboard. Remember, it's never to late to learn, and to get from good to great.
+ Bodyboarding News |