text:
Karim Benzema banned from France squad over sex tape blackmail
Karim Benzema looks set to miss next summer's Euro 2016 finals after he was banned from representing his country amid the ongoing investigation into an alleged attempt to extort money over a sex-tape.
Benzema has been declared as "no longer selectable" for the national team while facing provisional charges of conspiracy to blackmail, French football federation president Noel Le Graet has announced.
The Real Madrid forward was interviewed by police in France on November 5 over his involvement in an alleged attempt to extort money from a tape that is reported to have been made of his France team-mate Mathieu Valbuena and his partner.
Le Graet, speaking at a press conference at FFF headquarters on Thursday afternoon, said the 27-year-old would not be considered for the national team while the investigation remained ongoing.
"(Benzema is) no longer selectable. If the situation has not changed in March, he will not be available for selection," Le Graet was quoted as saying by France Football.
"Karim Benzema is not selectable until the situation changes, until there is something new in this case.
"It's a decision I have taken, as president of the federation."
Le Graet stressed there was "no problem" with Lyon playmaker Valbuena, however as he added: "Mathieu Valbuena is the victim."
Quoted in L'Equipe, he continued: "For the last get-together, (France coach Didier) Deschamps did not take him because he was in turmoil. There is no problem with Valbuena.
"Valbuena has done nothing. At the time that he was made aware of the case, he did what he needed. He was very close to Benzema. There are hard times in friendship. But we must forgive. There will come a time when these two boys will one day chat."
Thursday's announcement puts Benzema's participation in Euro 2016 in serious doubt. Host nation France begin their campaign on June 10, after warm-up games against Holland and Russia in late March.
Benzema has scored 27 goals in 81 appearances for his country, and netted a hat-trick on Tuesday as Real Madrid hammered Malmo 8-0 in the Champions League.
Benzema's lawyer Alain Jakubowicz told RMC Sport towards the end of last month that the forward, who denies any wrongdoing, "was a positive, not a negative, intermediary" as he sought to put Valbuena in contact with his friend.
That followed an interview with Valbuena in Le Monde in which he said: "I am very, very, very disappointed and I can only say that my relations with Karim were not as sincere as he makes out."


text:
My friend Paul's wife, who suffered a heart attack and is on a ventilator.
Pray along with our community, or submit your own.The prayers on this page are also being prayed by The Episcopal Community
- Lena H.
Please pray for my family to find comfort and healing after the passing of my uncle, who was loved deeply and missed tremendously.
- Jerrie D
Prayer for healing for my father who has suffered a heart attack. He had one heart surgery on Friday and is scheduled for another tomorrow. He also is loosing blood and they can't locate the source.
- Daniel
Please pray that my faith will be strengthened and I will be able to believe in this faith again. I am struggling with believing in Christ.
- Emily M.
Dear Lord, Guide the leaders of all nations so that all wars shall cease. Let not the scourge of hatred spread throughout the World. Make us all instruments of your peace Amen
- Geoffroy AH
Almighty God, guide and protect my family during these hard times. Deliver us from these trying times, give us the strength to maintain our faith in you. Heal us Father and help us in all ways. In Jesus name I pray. Amen
- Richard H.
Please give me the strength, confidence and talents to do well in my new career. I am truly grateful for all of the blessings that you have given me this year. Thank you Lord.
May the Lord grant peace and happiness upon my grandmother, who is suffering from the very intense disease, Parkinson's. Thank you, Lord for blessing us with her presence on her 90th birthday, and for the slivers of hope you provide everyday.
- Rachel T.
Please, please pray as I try to get accepted into a school (last minute) this summer. I am waiting to hear back. It is very selective, and I would appreciate any prayers you could give. Peace.
- Read T.

subset: commoncrawl


text:
Multiconductor unshielded control, audio and computer cable. Tinned copper stranded cable, PVC insulation, chrome PVC jacket. Working voltage 600V.
Requires Adobe Acrobat Reader
22-3281 - Basic Electronic Tool Kit
Kit contains: Full range digital multimeter (similar to #72-6343), plastic parts box, 5" diagonal cutters, 5" long nose pliers, 6" slanted cutters, 6" long nose pliers, 6" stainless steel scissors, 7-in-1 wire cutters/crimpers, three Phillips screwdrivers (#0 x 75...
22-7980 - Thumb Winder Blued Steel Fish Tape
Compact and rugged fish tape features 50' of Ideal's exclusive Blued Steel tape for superior performance and rust resistance Blued Steel is constructed of the highest grade tempered steel for easier feeding into conduit, easier winding in, and winding ...
21-12280 - 80 LED Magnifier Lamp with Clamp Base - 7" Lens
Clamp-on magnifier lamp has a 35" swing arm that adjusts to various viewing angles. 80 LEDs provide bright balanced light which is helpful for a variety of desktop applications.
22-11109 - Punchdown Tool With Cable Stripper
Designed to strip twisted-pair UTP/STP data cables (Cat5, Cat 5e and Cat6) and terminate the wires into 110 blocks. It's fast and easy to use and will self-regulate strip depth. This tool can also be used on multi-pair cable, hook-up wire, and more.
Excellent f...
Order was ready for Will-Call pick-up when promised and all items and quantities were correct and in the bag! Smooth transaction. Thanks!


text: Much has been made about the appearance of Jacob in the season 5 finale entitled "The Incident." And it is obvious the he plays an essential role in the plot of the series as a whole, and in the season to come. My theory has a lot to do with the relationship between Jacob and the man he can be seen talking with in the black shirt that will hereafter be referred to as "Otherman." My theory also will make many references to the movie "Constantine" starring Keanu Reeves. If you have not seen it, I recommend it not only for the purpose of understanding this theory, but also because it is a great movie. So, basically I think that the storyline in Constantine and the overall story behind Lost are one in the same. In Constantine, Earth and humans are really just in the middle of a wager made between God and the Devil. The wager was for the souls of all mankind. The conditions of this bet were simple, no direct contact with humans, only indirect influence. You see, God believed that humans really were good in their hearts, while the Devil, obviously believed the opposite. Now I believe that the two characters seen in the opening moments of the season 5 finale (Jacob and Otherman) were God and the Devil respectively. And I believe that the reason for their being on Earth was to observe their wager. There was one line that really prompted this theory, when Otherman says "You brought them here to prove me wrong." And then goes on to say how humans only corrupt, pillage and destroy. Jacob replies by telling Otherman that he is wrong. I believe that they were talking about their bet. Then, Otherman goes on to say that one day he will find a loophole, to kill Jacob. A few other supporting connections, first, as I'm sure you're aware, John Locke from Lost shares a name with British Philosopher John Locke, who believed that people were inherently good. While Rousseau, also a European Philosopher, argued that people are selfish and violent by nature. This could be what the two men were talking about on the beach when Othermen said that Jacob just wanted to "prove him wrong" they could be talking about their bet, and the general soul of humanity. Next, the infamous loophole that Otherman claims to have finally found. In Constantine, the one condition of the bet is that neither side can have direct influence. In Lost we see Jacob having contact with many of the characters. But there is only one character that he has a direct impact on. Jacob brings John Locke back to life after being thrown out of a window. I would say that is direct contact, thus nullifying the bet between Jacob and Otherman. I believe this is the loophole that Otherman found, and what allowed Jacob to be killed. I am open to comments and questions, anyone have any thoughts?


text: 04:29 3 Years Retrieved from "http://channel101.wikia.com/wiki/3_Years?oldid=11882" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: 3 Years Failed Pilots CnR Productions Craig Morris Rob Potter Wes Eastin Robert Hayes Cole Hostetler Derek Morris Add category Cancel Save


text:
ROEHSOFT RAM Expander (SWAP) 3.42 Patched Proper Android Apk Download
**ROEHSOFT RAM Expander (SWAP) 3.42 Patched or Crack is here to Download Direct**
ROEHSOFT RAM Expander :
Please check your device for compatibility before you purchase this app with
'MemoryInfo & Swapfilecheck' to find it see my other apps.
This is the most powerful Release ever! Exclusive only here in Play Store!
Insufficient RAM, memory is too small? Use your SD card as a working memory expansion! A Memory Manager wich make's you life more easy as you think…
A great programmer once said to insufficient RAM -RAM only helps-. Convince yourself how right this man had.
Finally, more memory with a click! Memory from Android 1.6 up with root access and external SD card! More memory means that background tasks will never more automaticaly terminated, and many programs will work correctly in the first place!
On many devices, there are problems with games require a lot of memory, this fixes the problems RAMEXPANDER. And they can play latest games on devices that otherwise would not be able to start such APPs. No more out of memory! No more memory is full!
Languages: English and German
Note: please try before you buy with our app "https://play.google.com/store/apps/details?id=com.roehsoft.meminfo" whether their device ROEHSOFT RAM Expander is compatible, you!
– Free SD card memory as a RAM use (SWAP RAM / SWAP MEMORY)
– Swapfile RAM expansion up to 4.0 GB (file system limit)
– No limit on SWAP partition!
– The usual performance degradation when paged not occur with sd card from class-8
– Widget for PNP swap (swap on / off swap)
– Detailed Memory Information & Analysis
– Autorun
– Swappiness kernel parameter set
– Easy foolproof use
(1 click optimization and automatic calculation)
– Supporting Tung all Android devices (root access and Kernelswap support)
Note: please try before you buy with our app "https://play.google.com/store/apps/details?id=com.roehsoft.meminfo" whether their device ROEHSOFT RAM Expander is compatible, you!
Should it come to problems please contact me before they write such queries to review forum!
not enough memory? equal to no more! More games to play and run more applications simultaneously! All you have to only increase your memory. And up to 4 GB! Larger memory, instead of using task killer or memory optimizer.
ROEHSOFT Ram Expander is more effective than any other tool of its kind Why? The First find out!
ROEHSOFT RAM expander support via a widget at lightning speed and off of extended memory.
This way you can remove the SD card despite swapfile or deploy via USB.
Also, you can important, elementary the swap kernel parameters even control the effectiveness of extended memory increase.
Size: 5.4 MB
Version: 3.42 Patched
Download Servers


text:
Barry LewLeominster, Massachusetts, US
English (North American), English
British, North American, US New England (Boston, Providence), US New York (New Jersey, Bronx, Brooklyn), Yiddish
Middle Aged
Special Skills
Audiobooks, Business, Cartoons, Documentaries, Educational, Internet, Jingles, Podcasting, Radio, Telephone, Television
Payment Terms
Hire Barry as a voice actor. Payment is made through Voices.com SurePay, an escrow service that guarantees your work is done to your satisfaction. Send payment securely by Visa, Mastercard or PayPal through Voices.com then download your files from the website.
Watch a video to see how to make a payment
Next Steps
To contact Barry Lew about your project, request a quote today. We'll walk you through the process step-by-step. It's fast and easy.
This talent has not uploaded any demos yet.
Title of Your New Demo 7777 Listens
Hire Barry Lew as a voice actor. Working with Barry Lew is fast and easy. We'll walk you through the process step-by-step.
Request a quote for your project today.


text:
Full Vintage Movie
Carmen (1998) FULL VINTAGE MOVIE
Reds (1997) FULL VINTAGE MOVIE
Avventura in Discoteca (1993) FULL VINTAGE MOVIE
Cronaca Nera 2 (1994) FULL VINTAGE MOVIE
SNATCHED WOMEN (Dyanne Thorne) Vintage Full Cult Movie
La Carovana della Violenza (1999) FULL VINTAGE MOVIE
Mia Moglie Aperta a Tutti (1990) FULL VINTAGE MOVIE
Let's Talk Sex (1982) FULL VINTAGE MOVIE
Photo amateurs vintage gay full length When a kinky lad boy needs some
La Signora In Cadillac Col Nero Dietro FULL VINTAGE MOVIE
Fisting Fun 102 (full movie)
19 Movie 63
Free gay boy kinky sex stories not full movie for teen
Young gay man fucking hot small boy movie full length Foot fun and a harsh sticking is in
Still dreaming about this movie of Vintage amateur movie from the forest
Kinky vintage threesome
Vintage Fun
Anal movie boys movie gay full length Clint
hot gf gets full mouth of cum movie movie 2
TrafficHolder.com - Buy and Sell Adult Traffic|Trafficshop.com - Let your business grow|Contact Us|Webmaster
All content, including images, text, graphics, video and audio content contained in the website is protected under the laws of copyright, owned or under license to company or its designees,and represents proprietary and valuable intellectual property.
Contact Webmaster 18 U.S.C. 2257 Record-Keeping Requirements Compliance Statement
Powered by Stream Rotator


text:
Chiwa Saitō (斎藤 千和 Saitou Chiwa; born March 12, 1981 in Saitama Prefecture, Japan) is a Japanese voice actress. She voiced Jean Greyerl in the Japanese version of Professor Layton vs. Phoenix Wright: Ace Attorney.
External linksEdit
|Pleeeeeeeease expand meeeeeeee!
|This article is a stub or is otherwise incomplete. You can help the Ace Attorney Wiki by expanding it.


text:
Gods of Fire and Light exist in the belief system of Ashra, Vuh and Elim.
It is believed that the first generation of the younger gods created by Ashra were the Gods of Fire and Light. The chief of those gods worshipped on Titan are Glantanka, Filash and Lord Moon/Lunara.
See AlsoEdit


text:
Need a Blood Titer in Cape Coral, FL? Simply order online 24/7 and get a fast, affordable Blood Titer at a lab near you (Find More Locations):
Why would I get a Blood Titer?
A Blood Titer is a blood test that checks the titer level. People in Cape Coral, FL order the Blood Titer to demonstrate immunity to certain diseases.
How much does a Blood Titer cost?
Our Blood Titer prices include the doctor's order that you need to get tested in Cape Coral, FL, all lab fees and taxes, and a pdf copy of your results. For current prices, please CLICK HERE.
What does a Blood Titer lab report look like?
For a popular Blood Titer lab report, please CLICK HERE.
We are delighted to offer the Blood Titer in Cape Coral, FL.
Blood Titer in other cities near Cape Coral, FL:Alva | Bokeelia | Bonita Springs | Captiva | Estero | Fort Myers | Fort Myers Beach | Lehigh Acres | Murdock | North Fort Myers | Pineland | Punta Gorda | Saint James City | Sanibel


text:
A recently built hotel in the centre of Athens, the Novus City Hotel boasts a superb location for those looking to explore the fabulous attractions of the city in the hip area of Metaxourgio and is only a few steps from the metro station. This 4* hotel features a great range of modern and stylish rooms with various accommodation to suit almost any guest and offers a number of excellent facilities and services that all help to ensure guests have an enjoyable and comfortable stay. Up on the roof/top floor of the building you can find the hotel's lovely pool is the ideal spot to refresh yourself or you can relax on the terrace and enjoy a selection of refreshing drinks and snacks from the rooftop bar. On the lower floors of the hotel you can find a comfortable bar and lounge area as an alternative to the rooftop bar and business users will find the concierge services and Wi-Fi internet available throughout the hotel very convenient. The hotel is also one of the few in the city that has a 3 level indoor and underground parking facility that is free to use for all hotel guests. The hotel staff and reception will be more than willing to help with any request about your stay as well as offer useful suggestions on some of the best places to eat or visit in the city.
Athens is the perfect place to spend a holiday if you are looking for shops and many interesting places to visit. With the hotel situated within walking distance to some great locations such as Omonia Square, Syntagma, Plaka, Monastiraki and Agora. The hotel is also close to one of the trendiest shopping areas of the city, Ermou Street where you can also find a great selection of designer shops as well as restaurants to visit or if you are looking for a more traditional and charming shopping experience you could visit the picturesque Monastiraki flea market just a few minutes away. Some of the many historical and cultural attractions that are well worth visiting during your stay in Athens might include the Metropolis Greek Orthodox Cathedral and there is one of the world's most famous historical monuments, the Parthenon is close to the hotel. Athens is also home to two UNESCO heritage sites with its ancient Acropolis you can see from the hotel and the impressive medieval Daphni Monastery, with all of this and more all accessible via the many forms of public transport to help you get around and explore this fabulous city.
Distance from Airport:
20 miles - Athens International
There are a total of 85 rooms at the hotel, which include 56 premium twin-bedded rooms, 5 deluxe double-for-single use rooms as well as 22 executive king size double or triple rooms and a junior suite along with executive suite to choose from. All the rooms feature double glazed sound proof windows to ensure you can enjoy peace and quiet and come with all the modern amenities you would expect from a hotel of this class including air conditioning, 22" LCD TV with satellite and pay TV channels, mini-fridge, Wi-Fi access, safety deposit box, direct dial telephone and modern bathrooms with shower or bathtub.
There are also separate smoking and non-smoking floors and room service is available 18 hours a day.
Transfer time:
40 minutes
Eating and Drinking:
A complimentary and varied buffet breakfast is provided each morning to all guests, with the cost included in your room rate and can be enjoyed in the air-conditioned breakfast room or terrace.
There are also 2 bars at the hotel providing great places to sit down with friends or family and enjoy a refreshing drink or range of snacks, deserts or ice cream. On the top floor along with the pool and terrace you can find the Views Rooftop Bar and on the lower floors is the Atrium Bar and Lounge.
Swimming pools:
There is a great swimming pool located at the top of the hotel where you can enjoy splendid views of the city and Acropolis and there is a wooden terrace perfect for relaxing and soaking up the sun.
Right choice:
The Novus City Hotel is the right choice if you are looking to stay in the centre of the cosmopolitan metropolis of city where you can easily visit many of its great attractions and sights, with the hotel providing pleasant and affordable accommodation and services that help to ensure a memorable holiday in Athens.
Suitable for:
Individuals and couples


text:
Raaz Reboot Vs Pink 5th Day Box Office Total Collection
Raaz Reboot Vs Pink 5th Day Box Office Total Collection,Raaz Reboot 5th day Box Office Collection Pink 5th Day Box Office Collection Pink Cast Raaz Reboot Cast facebook wiki twitter all datails on Boxofficetotalcollection.in
Raaz Reboot Vs Pink 5th Day Box Office Total Collection:It's simply an issue of day for the crowd to topple a's film industry rankings. Raaz Reboot highlighting Emraan Hashmi in a negative part indicated promising development on the principal day. Notwithstanding, the film by one means or another couldn't figure out how to keep the same force on taking after days while Amitabh Bachchan and Taapsee Pannu's Pink turned out from the chilly to wind up individuals' dear. Be that as it may, this is not to say Raaz Reboot is not doing great. Actually, the film has profited from the nearness of Emraan and additionally different components normal for a run of the mill Bhatt Camp film. It has melodies, new faces, excellent areas to counterbalance the normal ghastliness part. Pink, then, has figured out how to begin a civil argument on various stages. Pink, which got gradually on the main day, has in the long run picked up energy taking after a solid verbal exposure. As such, both Pink and Raaz Reboot are neck and neck in rivalry to win over the gatherings of people.
Raaz Reboot Vs Pink 5th Day Box Office Total Collection
The aggregate weekend gathering of Raaz Reboot is Rs 18.09 crore while Pink has so far gathered Rs 21.51 crore. This is too soon to anticipate the general execution of both the movies. Not at all like huge motion picture conflicts in the cinematic world, both Pink and Raaz Reboot focus on a specific sort of gathering of people. While Raaz Reboot is doing especially well in single screens, Pink is pulling in a corner crowd in multiplexes. Pink saw a solid development on Saturday, gaining Rs 7.65 crores, a wonderful hop from Rs 4.32 crores on Friday. On Sunday, the film made Rs 9.54 crore.
Exchange examiner Taran Adarsh tweeted, "#RaazReboot doesn't witness development on Sun… Single screens better… Fri 6.30 cr, Sat 5.49 cr, Sun 6.30 cr. Absolute: ₹ 18.09 cr. India biz."
Pink 5th day box office collection,Raaz Reboot 5th day box office collection,Pink Vs Raaz Reboot 1st Tuesday box office collection,Pink Vs Raaz Reboot 5th day worldwide box office collection


text:
Need a cheap blood test in Festus, MO? Simply order online and get a cheap blood test at a lab near you (Find More Locations):
What is a Cheap Blood Test?
A Cheap Blood Test is a blood test that checks your health in a low cost way. People in Festus, MO order a Cheap Blood Test for general screening or ongoing tracking.
How much does your Cheap Blood Test cost?
Our Cheap Blood Test prices include the doctor's order that you need to get tested in Festus, MO, all lab fees and taxes, and a pdf copy of your results. For current Cheap Blood Test prices, please CLICK HERE.
What does a Cheap Blood Test lab report look like?
For a sample report of a popular Cheap Blood Test panel in Festus, MO, please CLICK HERE.
In a time of rising healthcare costs, we can help people in Festus, MO get a Cheap Blood Test. We are delighted to offer our Cheap Blood Test service in Festus, MO.
Cheap Blood Test in other cities near Festus, MO:Barnhart | Bloomsdale | Crystal City | De Soto | French Village | Hematite | Herculaneum | Hillsboro | Kimmswick | Liguori | Mapaville | Pevely | Valles Mines | Valmeyer


text:
"More of" or "Moron" – The Mangru Report – Episode 18 October 22, 2010Posted by Admin in Panel Discussion.
Tags: 401k, 403b, Al Zucaro, Anthony Pulieri, banks, barack, Ben Bernanke, charles prince, citigroup, dan mangru, federal reserve, financials, obama, Palm Beach, president, quantitative easing, recession, recovery, retirement, Richard S. Bernstein, robert rubin, Social Security, The Mangru Report, United Bullion Group, world trade center
comments closed
Federal Reserve Chairman Ben Bernanke is ready to do whatever it takes to whatever it takes to support the struggling recovery, but has declined to say how bad things are.
President Obama's Economic Recovery Advisory Board has released their 8 recommendations for fixing the U.S. retirement system, but does it go far enough?
Citigroup's Charles Prince and Robert Rubin failed to disclose that the company was taking massive loan losses in the subprime market. Should they prosecuted?
Watch the Mangru Report Panel of Experts composed of Anthony Pulieri (United Bullion Group), Richard Bernstein (Richard S. Bernstein & Associates), and Al Zucaro (World Trade Center Palm Beach) discuss what these leading financial and political decision makers are doing and whether the U.S. deserves "more of" these people or whether they are acting like "morons".
This segment was sponsored by First Hour Trading, you can download their FREE Report, "How to make enough money in the first 59 minutes of the market" by CLICKING HERE NOW.
Dr. Larry Kotlikoff Interview with Dan Mangru – The Mangru Report on Fox Business October 9, 2010Posted by Admin in Interviews.
Tags: analysis, banking, banks, bernanke, boston, boston university, business, commentary, crash, dan mangru, debt, deficit, economic, economics, Fox, Fox Business, healthcare, industry, jimmy stewart, jimmy stewart is dead, kotlikoff, liabilities, mangru, medicaid, medicare, mutual fund, news, obama, professor, recession, Social Security, solutions, stability, talk, The Mangru Report, trillion, tv, unemployment
comments closed
As the debate goes on as to whether the U.S. banking system is stable and secure, Boston University Professor of Economics Dr. Larry Kotiikoff is proposing new solutions to change the way that we bank in his new book, "Jimmy Stewart is Dead". Watch Kotlikoff and Dan Mangru discuss limited purpose banking, how it can be implemented in our current system, how the government is exacerbating the problem, and how much money we really owe in debt and obligations.
Worried About Your Wealth? – Read This TODAY
New Poll: Was George W. Bush a better President than Barack Obama? – CLICK HERE TO VOTE
Download The Mangru Report App for your iPhone, iPad, or iPod Touch
Follow TheMangruReport on Facebook
Steve Forbes One-On-One Interview with Dan Mangru – The Mangru Report – Episode 12 August 18, 2010Posted by Admin in Dan Mangru, Interviews.
Tags: assassination, brazil, business, capitalism, censorship, china, dan mangru, Dollar, finance, Forbes, Fox, Fox Business, hyperinflation, Inc., india, inflation, magazine, malcolm, malcolm s. forbes, mangru, Realclearpolitics, Social Security, steve forbes, The Mangru Report, U.S.
comments closed
Steve Forbes is one of his generation's legacies of success, entrepreneurship, and wealth. He is currently the Chairman and CEO of Forbes Inc. and has expanded the company founded by his grandfather, B.C. Forbes, to become a global empire spanning from the U.S. to Europe to Asia & the Middle East. Needless to say that when Steve Forbes talks, people should listen, as he speaks with insights learned from both his family and his experiences.
During Freedom Fest 2010, Steve Forbes sat down with Dan Mangru for a private one-on-one interview that you can only see right here on The Mangru Report. In this nothing-held-back interview, Forbes answers the tough questions such as "Will Capitalism Hurt?", "Will Inflation Ever Come?", will the next century belong to China and Brazil, should investor's trade currency, the problems he's faced expanding the Forbes brand to places like India and Russia, media censorship in China, and how he's managed to live up to the expectations following the success of his father (Malcolm S. Forbes) and his grandfather (B.C. Forbes).
Episode Clips – The Mangru Report Episodes 8-11 July 12, 2010Posted by Admin in Dan Mangru, Panel Discussion.
Tags: Anthony Pulieri, armand grossman, atlanta, barcelona, bernanke, boehner, canada, Crist, dan mangru, euro-pacific capital, florida atlantic university, Germany, greece, jindal, john browne, mangru report, obama, pelosi, quebec, sacrifice, Social Security, south africa, spain, United Bullion Group, world cup
comments closed
We've received a couple of emails asking about when the clips from recent episodes will be posted online. We are happy to let everyone know that all clips from Episodes 8-11 are now up on our YouTube page. In the meantime, we will start posting the best clips throughout the week here on The Mangru Report website.
Episode 11 – Global Gains
Watch The Mangru Report Panel of Experts Discuss the Economic Impact of The World Cup
Episode 11 – "More Of" or "Moron"
Episode 11 – The Mangru Moment – On Sacrifice
Florida Senate President Mike Haridopolos To Appear As Guest Panelist on The Mangru Report TODAY at 5:30 p.m. May 29, 2010Posted by Admin in Panel Discussion.
Tags: amnesty, anthony, arizona, Auto, bailout, business, Capital, Charlie, commentary, Crist, dan mangru, deficit, euro, Euro-Pacific, florida, GM, gold, haridopolos, immigration, inflation, investments, john browne, Loan, mike, money, Payback, president, pulieri, report, retirement, ronald reagan, senate, senator, Social Security, taxes, United Bullion Group
comments closed
Incoming Florida Senate President Mike Haridopolos will be a guest panelist today on The Mangru Report. You can tune in to watch the show at 5:30 p.m. today and Sunday on Fox Business Network. Also appearing on the Mangru Report Panel of experts are John Browne of Euro-Pacific Capital, and Anthony Pulieri of United Bullion Group. During today's episode the panel will discuss sending tax dollars to Greece, the value of your home for retirement, and whether the U.S. dollar will remain the reserve currency.
Also in case you missed last week's episode, here's the panel discussions on Florida Governor Charlie Crist's immigration plan to save Social Security (Retirement Watch), and GM's government payback fraud (War on Your Dollar).


text:
|Publication number
|Publication type
|Application number
|Publication date
|Dec 27, 2011
|Filing date
|May 25, 2007
|Priority date
|May 25, 2007
|Fee status
|Also published as
|Publication number
|Peter J. Tarcha, David Pecosky
|Original Assignee
|Abbott Laboratories
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (15), Non-Patent Citations (8), Classifications (23), Legal Events (2)
|External Links: USPTO, USPTO Assignment, Espacenet
1. Field of Invention
The present invention relates to a one-step method for loading a drug coating onto an interventional device. Particularly, the present invention is directed to a method of mixing a drug with a phosphorylcholine-linked methacrylate polymer in a liquid and applying the mixture to an interventional device, such as a stent, in a single step.
2. Description of Related Art
Cardiovascular disease is prevalent in the United States and in other parts of the world. One manifestation of cardiovascular disease is atherosclerosis, which is the buildup of plaque (or fatty deposits) on the walls of blood vessels, such as coronary arteries. This buildup of plaque can grow large enough to reduce blood flow through the blood vessel. Serious damage results when an area of plaque ruptures and forms a clot, which travels to another part of the body. If the blood vessels that feed the heart are blocked, a heart attack results. If the blood vessels to the brain are blocked, a stroke results. Thus, atherosclerosis can be fatal for some people.
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating atherosclerosis. Angioplasty is the mechanical widening of an obstructed blood vessel. This procedure generally entails introducing a catheter assembly into the cardiovascular system of a patient via the brachial or femoral artery. Once introduced, the catheter assembly is advanced through the coronary vasculature until the balloon portion of the catheter assembly is positioned across an occlusive lesion. When positioned across the lesion, the balloon is inflated to a size sufficient to radially compress the plaque against the vessel wall. Subsequently, the balloon is deflated to allow the catheter assembly to be withdrawn from the vasculature of the patient.
While PTCA is widely used, it suffers from two unique problems. First, the blood vessel may suffer acute occlusion immediately after or within the initial hours after the dilation procedure. Such occlusion is referred to as "abrupt closure." Abrupt closure occurs in approximately five percent of cases in which PTCA is employed. The primary mechanisms of abrupt closures are believed to be elastic recoil, arterial dissection and/or thrombosis. The second problem associated with this procedure is the re-narrowing of an artery after an initially successful angioplasty. This re-narrowing is referred to as "restenosis," which among other things, typically occurs within the first six months after angioplasty. Restenosis is believed to be due to the proliferation and migration of cellular components from the arterial wall, as well as through geometric changes in the arterial wall referred to as "remodeling."
To overcome some of the drawbacks of angioplasy, such as reducing occlusion of the artery, thrombosis formation and/or restenosis, it is known to implant an expandable interventional device or prosthesis to maintain patency. One example is a stent. A stent is a mesh tubular member used to prop open a lumen. The stent is collapsed onto a catheter or stent delivery device and travels to the area of blockage while secured onto the catheter. The stent is positioned across the blockage or lesion and radially expands to prop open the blood vessel.
To better effectuate the treatment of atherosclerosis and other cardiovascular diseases, it is beneficial to load an intraluminal device or prosthesis with one or more therapeutic agents, such as antiproliferatives, for delivery to a lumen. One commonly applied technique for the local delivery of a drug to a stent, for example, is through the use of a polymeric carrier coated onto the surface of a stent, as disclosed in Berg et al., U.S. Pat. No. 5,464,650, the disclosure of which is incorporated herein by reference. Berg's method of loading drug onto the stent, however, requires multiple repetitive coating steps to achieve uniformity and control over the amount of therapeutic substance to be applied to the stent. Furthermore, Berg requires an evaporation step so that the coating of the final product includes the drug and polymer but little or no residual solvent.
Although conventional methods and products such as those taught by Berg generally have been considered satisfactory for their intended purpose. Such conventional methods are inefficient and costly due to the requirement of separate, multiple coating and time for sufficient evaporation. Additionally, each additional step of such conventional processes require additional manipulation of the stent being coated. Because stents are, by their very nature, fragile devices, additional manipulation increases the risk of physical damage and contamination of the stent. There thus remains a need for an efficient and economic method and system for loading a drug into a polymer coating for application to a stent with a minimum amount of manipulation of the stent or similar device and to allow for uniform distribution of the polymer coating.
To achieve these and other advantages the invention, an efficient method of making a drug eluting interventional device that requires less steps to achieve a device loaded with therapeutic agent, is provided. The method is not only more efficient because it requires less steps and material to achieve a drug eluting interventional device, excessive manipulation of the interventional device during the process is not necessary because the device can be sufficiently coated in one step.
The method comprises providing an interventional device having a bare surface and mixing at least one therapeutic agent and at least one polymer in a liquid to form a mixture. The mixture is applied to a portion of the bare surface of the interventional device to form a coating. Advantageously, no base coating is applied to the stent.
The polymer component of the mixture may be a crosslinkable polymer, such as phosphorylcholine-linked methacrylate polymer. The polymer, may further include a trimethoxysilane functional group. The polymer or polymers and at least one therapeutic agent may be mixed using ethanol as the liquid.
The therapeutic agent component of the mixture may be a variety of therapeutic agents. The term "therapeutic agent" as used herein, refers to any compound, mixture of compounds, or composition of matter consisting of a compound, which produces a therapeutic or useful result. For example and as will be discussed below. The therapeutic agent can be a polymer, a marker, such as a radiopaque dye or particles, or can be a drug, including pharmaceutical agents, or an agent including inorganic or organic drugs without limitation. The therapeutic agent can be in various forms, such as uncharged molecules, components of molecular complexes, pharmacologically acceptable salts such as hydrochloride, hydrobromide, sulfate, laurate, palmitate, phosphate, nitrate, borate, acetate, maleate, tartrate, oleate, and salicylate.
The coated interventional device may include about 10 to about 13 micrograms of therapeutic agent along a linear millimeter of the length of the device or as needed for the desired end product. The coating may include 30% by weight of the therapeutic agent or agents relative to the polymer or as needed for the desired end product. Also, the coating may include a uniform matrix of therapeutic agent and polymer. Any number of drug-to-polymer ratios may be used depending on the desired properties of drug release and polymer functional attributes such as flexibility, biodegradability, adhesiveness, etc.
A variety of methods can be utilized to apply the mixture to the bare surface of the interventional device. For example, spraying, dipping, jetting, or any other coating application techniques can be used.
The mixture can be uniformly applied to at least a portion of the interventional. In this regarding the entire surface of the interventional device can be coated or only a section of the interventional device can be coated if desired. Also, the therapeutic agent or agents may be uniformly distributed in the coating, or layered or otherwise disbursed or dissolved in or on the coating or coatings. The coating may have a thickness of about 5 to about 6 microns.
The method may include curing the coated interventional device, such as by heating. If desired, the method may include applying an overcoating to at least a portion of the stent.
The coated stent may be mounted to a delivery device and sterilized. The sterilization of the coating stent may include irradiating the coating. The coated stent may be dried before being sterilized or otherwise processed as desired. Additionally, the sterilizing step may facilitate crosslinking of the polymer coating. The sterilizing step may include exposing the coated stent to at least one cycle of ethylene oxide or heat.
The interventional device can be, for example, a self-expandable or balloon-expandable stent, a graft, filter, or balloon.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and are intended to provide further explanation of the invention claimed.
Reference will now be made in detail to the present embodiments of the invention. The method and corresponding steps of the invention will be described in conjunction with the detailed description of the system.
The methods and products presented in this disclosure may be used for achieving an eluting interventional device, such as a drug eluting stent or balloon. The present invention is particularly suited for preparing drug eluting interventional devices in which the drug is loaded onto the interventional device in one step.
The method generally includes mixing at least one therapeutic agent and at least one polymer in a liquid to form a mixture. The mixture is applied to a bare surface of the interventional device. The application step may include selectively coating a surface of the interventional device. In this regard, the entire surface of the interventional device can be coated or alternatively, only predetermined selections of the interventional device can be coated. In this manner, a mask can be used if a selected coating pattern is desired. The application step can include coating the surface of the interventional device by various techniques, such as spray coating, dipping, or jetting, or other art-known application techniques.
In one embodiment, the mixture includes a crosslinkable polymer, such as a phosphorylcholine-linked methacrylate polymer. The phosphorylcholine-linked polymer can include one or more trimethoxysilane functional groups. It is believed that the trimethoxysilane functional group allows crosslinking of the polymer. Alternatively, a linear phosphorylcholine polymer can be used. The polymer is mixed in a liquid, such as ethanol.
Additionally, a therapeutic agent is mixed in the liquid with the polymer such that a polymer-therapeutic agent liquid mixture is formed. In one embodiment, the therapeutic agent and the polymer is mixed in a common solvent, such as ethanol. The mixture is applied to a surface of the interventional device in one step to form a therapeutic agent loaded coating on the interventional device. Advantageously, repetitive coating steps are not required to achieve a drug eluting interventional device.
The coating layer can be applied to the surface of the interventional device such that a thickness of about 5 to 6 microns in thickness is achieved. If desired, an overcoating layer may be applied to the coating layer. For example, the overcoating layer can be an uncrosslinked phosphorylcholine polymer.
The method can further include a curing step during which the coated interventional device is cured. In one embodiment, the curing included heat curing the coated interventional device. In one example, the a mixture of ABT-578 and phosphorylcholine-linked methacrylate polymer is applied to the a stent. The coated stent is cured by heating at about 70 degrees Celsius for about four hours. Importantly, the drug is stable and does not substantially degrade during the heat curing step.
The method can further include a sterilizing step. In this regard, the interventional device may be mounted to a delivery device and sterilized by irradiating the coated interventional device. The sterilizing may include exposing the coated interventional device to at least one cycle of ethylene oxide.
In an embodiment of the present invention, a stent is loaded with therapeutic agent such as ABT-578 with polymer, overcoated with non-crosslinked phosphorylcholine polymer, and mounted on a balloon. The stent is then subjected to ethylene oxide (ETO) sterilization. ETO sterilization is a high humidity (>40% RH) process done at room or elevated temperature (20-60 degrees C.). The ETO cycle results in crosslinking of the overcoating phosphorylcholine polymer.
A variety of therapeutic agents are suitable for coating the interventional device. Moreover, a combination of therapeutic agents can be used. For example, the therapeutic agent may be rapamycin or a derivative or analog thereof.
As noted above, the interventional device is at least partially loaded with therapeutic agent. In an embodiment of the invention, at least one therapeutic agent can be selected from but not limited to anti-proliferative, anti-inflammatory, antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombotic, antimitotic, antibiotic, antiallergic and antioxidant compounds. For example, the therapeutic agent can be a pharmaceutical agent or drug such as rapamycin or a derivative or analog thereof. According to the McGraw-Hill Dictionary of Scientific and Technical Terms, Fifth Edition, an analog is "[a] compound whose structure is similar to that of another compound but whose composition differs by one element," and a derivative is "a substance that is made from another substance." These definitions are adopted throughout this document.
The therapeutic agent may be a synthetic inorganic or organic compound, a protein, a peptide, a polysaccharides and other sugars, a lipid, DNA and RNA nucleic acid sequences, an antisense oligonucleotide, an antibodies, a receptor ligands, an enzyme, an adhesion peptide, a blood clot agent including streptokinase and tissue plasminogen activator, an antigen, a hormone, a growth factor, a ribozyme, a retroviral vector, an anti-proliferative agent including rapamycin (sirolimus), 40-O-(2-hydroxyethyl)rapamycin (everolimus), 40-O-(3-hydroxypropyl)rapamycin, 40-O-(2-hydroxyethyoxy)ethylrapamycin, 40-O-tetrazolylrapamycin (zotarolimus, ABT-578), paclitaxel, docetaxel, methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride, and mitomycin, an antiplatelet compound, an anticoagulant, an antifibrin, an antithrombins including sodium heparin, a low molecular weight heparin, a heparinoid, hirudin, argatroban, forskolin, vapiprost, prostacyclin, a prostacyclin analogue, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, a thrombin inhibitor including Angiomax�, a calcium channel blocker including nifedipine, colchicine, a fibroblast growth factor (FGF) antagonist, fish oil (omega 3-fatty acid), a histamine antagonist, lovastatin, a monoclonal antibodies, nitroprusside, a phosphodiesterase inhibitor, a prostaglandin inhibitor, suramin, a serotonin blocker, a steroid, a thioprotease inhibitor, triazolopyrimidine, a nitric oxide or nitric oxide donor, a super oxide dismutase, a super oxide dismutase mimetic, estradiol, an anticancer agent, a dietary supplement including vitamins, an anti-inflammatory agent including aspirin, tacrolimus, dexamethasone and clobetasol, a cytostatic substance including angiopeptin, an angiotensin converting enzyme inhibitor including captopril, cilazapril or lisinopril, an antiallergic agent including permirolast potassium, alpha-interferon, bioactive RGD, and genetically engineered epithelial cells. Other therapeutic agents which are currently available or that may be developed in the future for use with implantable medical devices may likewise be used and all are within the scope of this invention.
Examples of such antithrombotics, anticoagulants, antiplatelet agents, and thrombolytics include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapriprost, prostacyclin and prostacylin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa (platelet membrane receptor antagonist antibody), recombinant hirudin, and thrombin inhibitors such as Angiomax�, from Biogen, Inc., Cambridge, Mass.; and thrombolytic agents, such as urokinase, e.g., Abbokinase� from Abbott Laboratories Inc., North Chicago, Ill., recombinant urokinase and pro-urokinase from Abbott Laboratories Inc., tissue plasminogen activator (Alteplase� from Genentech, South San Francisco, Calif. and tenecteplase (TNK-tPA).
Examples of such cytostatic or antiproliferative agents include rapamycin and its analogs such as everolimus, ABT-578, i.e., 3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23 S,26R,27R,34aS)-9,10,12,13,14,2-1,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(-1S,3R,4R)-3-methoxy-4-tetrazol-1-yl)cyclohexyl]-1-methylethyl]-10,21-dimet-hoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyc-lohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone; 23,27-Epoxy-3H pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone, which is disclosed in U.S. Pat. Nos. 6,015,815, 6,329,386, U.S. Publication 2003/129215, filed on Sep. 6, 2002, and U.S. Publication 2002/123505, filed Sep. 10, 2001, the disclosures of which are each incorporated herein by reference thereto, tacrolimus and pimecrolimus, angiopeptin, angiotensin converting enzyme inhibitors such as captopril, e.g, Capoten� and Capozide� from Bristol-Myers Squibb Co., Stamford, Conn., cilazapril or lisinopril, e.g., Prinivil� and Prinzide� from Merck & Co., Inc., Whitehouse Station, N.J.; calcium channel blockers such as nifedipine, amlodipine, cilnidipine, lercanidipine, benidipine, trifluperazine, diltiazem and verapamil, fibroblast growth factor antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin, e.g. Mevacor� from Merck & Co., Inc., Whitehouse Station, N.J. In addition, topoisomerase inhibitors such as etoposide and topotecan, as well as antiestrogens such as tamoxifen may be used.
Examples of such anti-inflammatories include colchicine and glucocorticoids such as betamethasone, cortisone, dexamethasone, budesonide, prednisolone, methylprednisolone and hydrocortisone. Non-steroidal anti-inflammatory agents include flurbiprofen, ibuprofen, ketoprofen, fenoprofen, naproxen, diclofenac, diflunisal, acetaminophen, indomethacin, sulindac, etodolac, diclofenac, ketorolac, meclofenamic acid, piroxicam and phenylbutazone.
Examples of such antineoplastics include alkylating agents such as altretamine, bendamucine, carboplatin, carmustine, cisplatin, cyclophosphamide, fotemustine, ifosfamide, lomustine, nimustine, prednimustine, and treosulfin, antimitotics such as vincristine, vinblastine, paclitaxel, e.g., TAXOL� by Bristol-Myers Squibb Co., Stamford, Conn., docetaxel, e.g., Taxotere� from Aventis S.A., Frankfort, Germany, antimetabolites such as methotrexate, mercaptopurine, pentostatin, trimetrexate, gemcitabine, azathioprine, and fluorouracil, and antibiotics such as doxorubicin hydrochloride, e.g., Adriamycin� from Pharmacia & Upjohn, Peapack, N.J., and mitomycin, e.g., Mutamycin� from Bristol-Myers Squibb Co., Stamford, Conn., agents that promote endothelial cell recovery such as Estradiol.
A therapeutic agent that is water insoluble can be used in a form that is a water-soluble derivative thereof to effectively serve as a solute, and on its release from the device, is converted by enzymes, hydrolyzed by body pH, or metabolic processes to a biologically active form. Additionally, the agents or drug formulations can have various known forms such as solutions, dispersions, pastes, particles, granules, emulsions, suspensions and powders. The drug or agent may or may not be mixed with polymer or a liquid as desired.
While the foregoing therapeutic agents are known for their preventive and treatment properties, the substances or agents are provided by way of example and are not meant to be limiting. Further, other therapeutic agents that are currently available or may be developed are equally applicable for use with the present invention.
If desired or necessary, the therapeutic agent can include a binder to carry, load, or allow sustained release of an agent, such as but not limited to a suitable polymer or similar carrier. The term "polymer" is intended to include a product of a polymerization reaction inclusive of homopolymers, copolymers, terpolymers, etc., whether natural or synthetic, including random, alternating, block, graft, branched, cross-linked, blends, compositions of blends and variations thereof. The polymer may be in true solution, saturated, or suspended as particles or supersaturated in the therapeutic agent. The polymer can be biocompatible, or biodegradable.
For purpose of illustration and not limitation, the polymeric material may include phosphorylcholine linked macromolecules, such as a macromolecule containing pendant phosphorylcholine groups such as poly(MPCw:LMAx:HPMAy:TSMAz), where MPC is 2-methacryoyloxyethylphosphorylcholine, LMA is lauryl methacrylate, HPMA is hydroxypropyl methacrylate and TSMA is trimethoxysilylpropyl methacrylate, and w, x, y, and z are molar ratios of the monomers used in the feed. These values are typically 23, 47, 25, and 5, respectively, but they are not necessarily the ratios that exist in the finished polymer. The polymer is herein referred to generally as "PC polymer."
The therapeutic agent can include a liquid. The liquid can be any single solvent or a combination of solvents. For purpose of illustration and not limitation, examples of suitable solvents include water, aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, ketones, dimethyl sulfoxide, tetrahydrofuran, dihydrofuran, dimethylacetamide, acetates, and combinations thereof. Preferably, the solvent is ethanol. More preferably, the solvent is isobutanol. Additionally, in another aspect of the invention, multiple therapeutic agents are dissolved or dispersed in the same solvent. For purpose of illustration and not for limitation, dexamethasone, estradiol, and paclitaxel are dissolved in isobutanol. Alternatively, dexamethasone, estradiol, and paclitaxel are dissolved in ethanol. In yet another example, dexamethasone, estradiol, and ABT-578, i.e., the rapamycin analog, 3S,6R,7E,9R,10R,12R,14S,15E,17E,-19E,21S,23-S,26R,27R,34aS)9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-3-methoxy-4-tetrazol-1-yl)cyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-2-3,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,-6H,3H)-pentone; 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontin-e-1,5,11,28,29(4H,6H,31H)-pentone, are dissolved together in one solvent. Preferably, the solvent is ethanol or isobutanol. Ethanol is more preferable for spray coating of the mixture and isobutanol is more preferable for jetting of the mixture.
Additionally, the therapeutic agent includes any of the aforementioned drugs, agents, polymers, and liquids either alone or in combination.
As used herein "interventional device" refers broadly to any device suitable for intraluminal delivery or implantation. For purposes of illustration and not limitation, examples of such interventional devices include stents, grafts, stent-grafts, filters, balloons, and the like. As is known in the art, such devices may comprise one or more prostheses, each having a first cross-sectional dimension or profile for the purpose of delivery and a second cross-sectional dimension or profile after deployment. Each prosthesis may be deployed by known mechanical techniques such as balloon expansion deployment techniques, or by electrical or thermal actuation, or self-expansion deployment techniques, as well known in the art.
The stent can be in an expanded or unexpanded state during the loading of therapeutic agent. The underlying structure of the stent can be virtually any structural design and the interventional device can be composed any suitable material such as, but not limited to, stainless steel, "MP35N," "MP20N," elastinite (Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, polymer, ceramic, tissue, or combinations thereof. "MP35N" and "MP20N" are understood to be trade names for alloys of cobalt, nickel, chromium and molybdenum available from Standard Press Steel Co., Jenkintown, Pa. "MP35N" consists of 35% cobalt, 35% nickel, 20% chromium, and 10% molybdenum. "MP20N" consists of 50% cobalt, 20% nickel, 20% chromium and 10% molybdenum. The stent can be made from bioabsorbable or biostable polymers. In some embodiments, the surface of the interventional device can include one or more reservoirs or cavities formed therein, as described further below.
The stent can be fabricated utilizing any number of methods known in the art. For example, the stent can be fabricated from a hollow or formed tube that is machined using lasers, electric discharge milling, chemical etching or other known techniques. Alternatively, the stent can be fabricated from a sheet that is rolled into a tubular member, or formed of a wire or filament construction as known in the art. Examples of such for purpose of illustration include U.S. Pat. No. 4,733,665 to Palmaz; U.S. Pat. No. 6,106,548 to Roubin et al.; U.S. Pat. No. 4,580,568 to Gianturco; U.S. Pat. No. 5,755,771 to Penn et al.; and U.S. Pat. No. 6,033,434 to Borghi, all of which are incorporated herein by reference.
In another embodiment, the interventional device can be a balloon. The balloon can be formed from a polymer tubular member. The polymer can be selected from a variety of materials including nylon, Pebax�, Hytrel� or a blend thereof. Additionally, other materials can be used if desired.
Uncrosslinked phosphorylcholine polymer provided as a dry powder. 1.0 gram of phosphorylcholine polymer powder was placed into each of three 3.5″�8″ Tyvec pouches designed for use as containers in radiation and ethylene oxide (ETO) sterilization experiments. The first pouch was subjected to one complete ETO cycle, including preconditioning. The second pouch was subjected to two ETO cycles, and the third pouch was subjected to three complete cycles. Subsequently, the samples were transferred to glass vials and placed in refrigerated storage. Each cycle involved preconditioning of the sample before the introduction of ETO for approximately 12 hours at 46 degrees Celsius under a relative humidity of 65%. The sample experiences ETO at 6 psi for about 5 hours at 46-50 degrees Celsius.
After the ETO sterilization process the sample that had undergone three cycles was prepared for NMR analysis. A weight of 20 mg were dissolved in 1.6 ml of deuterated chloroform containing TMS as a reference, by shaking on a wrist action shaker overnight. The presence of insolubles was noted in the sample after the solvent dissolution by a cloudy layer that creamed to the surface. The cloudy layer had a particulate consistency like silica gel swollen by a solvent, and was not suitable for solution-state NMR. The clear bottom layer was used for analysis. Samples that were not ETO-sterilized dissolved completely under these conditions demonstrating that the ETO process caused insolubles to form, due to crosslinking of the silane functionalities.
50 mg samples of phosphorylcholine polymer that had been subjected to 0, 1, 2, and 3 ETO cycles were separately dissolved in 1 ml of chloroform and shaken overnight. After shaking, the samples were allowed to stand. Cloudy layers creamed to the surface of the treated samples. The untreated sample was totally clear. The sample that was subjected to 1 cycle had a cloudy layer that was of greater volume than that of the 2 and 3 cycle samples, but slightly less concentrated as evidenced by less intense visible light scattering. In duplicate, additional 50 mg samples from each of the runs corresponding to 1, 2, and 3 ETO cycles were dissolved in 1 ml of chloroform and shaken overnight. Once again the insoluble material creamed to the top. The bottom solvent layer was removed and the insolubles were extracted three additional times with 2 ml aliquots of ethanol. In ethanol the insolubles settled to the bottom of the vials and the clear top layers were removed during the extraction process. After the third extraction, the samples were transferred completely as a suspension in ethanol to pre-weighed scintillation vials and dried in an oven overnight at 70 degrees Celsius. Based on the weights of the vials it was found that 1, 2, and 3 ETO cycles caused 67%, 75%, and 83% respectively, of the phosphorylcholine material to become insoluble particulates.
The sample that was subjected to three ETO sterilization cycles was used for the spectroscopic analysis because any changes or by-products due to the sterilization cycles would be magnified to the greatest extent in this sample. Control samples were unmodified phosphorylcholine polymer that never experienced preconditioning or ETO. The NMR results generated spectra that were consistent with the known structure of the phosphorylcholine polymer in both the native unsterilized polymer and the ETO processed polymer. Chemical changes to the polymer or residuals as a result of the ETO sterilization process were not evident in any of the spectra run on ETO processed material. This is not surprising because the crosslinking monomer is present at only 5% and silicone bond formation results in changes 2 bonds away from the nearest carbon, a longer range and less sensitive effect in NMR.
The infrared analysis indicated that the spectra, run in duplicate, obtained from the ETO treated sample are very similar to the spectra obtained from the control sample. Small differences were noted in the 800-900 cm−1 region.
Phosphorylcholine polymer from the same batch as was used for the ETO process experiments was used to determine the effects of heat curing. Three glass scintillation vials were flamed and cooled to eliminate moisture and weighed on an analytical balance. Approximately 200 mg of phosphorylcholine polymer was added to each vial and the vials were reweighed. A volume of 1 ml of ethanol was added to each vial and the contents shaken on a wrist action shaker for 20 minutes to form a solution. The caps of the vials were then removed and the ethanol allowed to evaporate overnight. A film of polymer was evident on the bottom of the vials. The vials were put into an oven at 70 degrees Celsius for 4.25 hours, to approximate the typical heat-curing conditions previously used with drug-eluting stent (DES) preparation. The vials were then removed and 5 ml of ethanol was added, and then shaken for 30 minutes. The presence of insolubles was not evident. The extracts were removed and placed in pre-weighed vials and the solvent was evaporated at 70 degrees Celsius to visible dryness followed by 111 degrees Celsius for 2 hours to remove all traces of ethanol. Reweighing the vials containing the extracts indicated that 89, 60, and 73% respectively of the samples had gone into the extraction solvent after the first extraction. The data indicated that 1 ETO cycle produced more insolubles than the currently used heat-curing due to more complete crosslinking.
To 88 grams (111 ml) of ethanol was added 4.0 grams of ABT-578 and 8.0 grams of phosphorylcholine polymer. The mixture was mixed to form a stock solution. A 15 mm coronary stent requires 150 micrograms of ABT-578 and therefore needed to obtain 6.33 microliters of solution to give the proper dosage of drug. By weighting, the stent needed to obtain 450 micrograms of solids. If a reagent jetter is used to dispense the drug and the process is 75% efficient and the droplet size is 50 microns, the jetter needs to be programmed to jet 129,052 drops per stent. After the required amount of solution is applied to the stent and the stent is dried, it is mounted on a balloon and subjected to 1 ETO sterilization cycle to complete the process.
Weighed 129 mg of ABT-578, a rapamycin derivative and 280 mg of phosphorylcholine-linked methacrylate terpolymer PC1036 and dissolved them in 10 ml of 100% by shaking overnight protected from light. The solution was filtered through a 0.45 micron Teflon filter and the solution was added to the syringe reservoir of a semi-automated spray atomization gun coupled to a lathe-like device designed to hold stents, rotate them and translate them linearly in front of the spray gun. The equipment was programmed to spray enough solution in order to obtain about 10 micrograms of drug per linear mm of stent length, taking into account the losses of solution due to lack of contact with the stent as it is sprayed. After spraying, the stents were allowed to dry in air, followed by packaging them individually in glass vials sealed with an ETO permeable Tyvec membrane. The samples were sent out for ETO sterilization by one or three complete cycles.
Analysis was done of the total drug level from 5 stents that underwent 1 ETO cycle and 5 stents that underwent 3 ETO cycles using standard extraction and HPLC analysis. It was found that the amount of drug in stents that underwent 3 cycles was approximately the same as in those that underwent 1 cycle, an indication that the drug was stable to 3 ETO cycles. The 15 mm and 18 mm stents had an average dosage of ABT-578 of 191 and 188 micrograms respectively with an 18% standard deviation.
Ten ABT-578 DES samples were tested. Five of the stents experienced one ETO sterilization cycle while the remaining five stents completed three ETO cycles, including three preconditioning steps. The stents were spray loaded with phosphorylcholine and ABT-578 at 32% drug relative to the phosphorylcholine (w/w). Twenty-four hour release curves were requested for the samples using a 1% Solutol media. All of the samples had remaining ABT-578 on the stents at the 24 hour time point. The samples that had finished only one ETO cycle eluted faster (approximately 80% at 24 hours) than the three cycle ETO samples (approximately 70% at 24 hours), suggesting that the 3 cycle samples retained the drug on the stent more robustly over the 24 hour time period.
Stents were observed under a stereomicroscope after dissolution and after extraction with 50% acetonitrile. Detachment of the coating during this dissolution process appears evident by the presence of filaments that coexist with and are intertwined in the struts after the dissolution period ends. These filaments are not present at the start of the experiment and the stent looks quite cosmetically pleasing. After extraction with 100% acetonitrile, no filaments were evident indicating that they detached completely.
The example was done to compare the delamination potential of both the Zomaxx DES and the stents coated in one step by the methods and with the compositions of the present invention. 224 ml of 100 pig serum was placed into centrifuge tubes and spun at 3500 RPM for 10 minutes. A cloudiness creamed to the surface along with a few large flakes of white material. The extraneous white materials and cloudy layers were removed by decanting with the assistance of a spatula during decantation. The bottom layers in the tubes were retained for a total volume of 170 ml. A volume of 0.8 ml of concentrated sodium azide solution in distilled water was added to the serum to give it a concentration of 0.01% to prevent microbial growth.
Two Zomaxx drug eluting coronary stents of 3.0 mm�18 mm were expanded and freed from their balloons. They were placed in 20 ml scintillation vials. They were photographed under the stereoscope and were found to exhibit no evidence of coating detachment. 10 ml of the pig serum was added to each vial and they were placed in a shaker (air heated incubator, Labline, 27 degrees C., 100 RPM) for 3 days. The stents rested gently on the bottom of the vials. After the incubation, the stents were rinsed once with PBS to prevent protein precipitation and remove loosely adhering protein and rinsed a second time with distilled water. No obvious evidence of coating detachment was seen.
The same process was performed on two stents that had been coated by the one step process of this invention. One stent had experience 1 ETO cycle and the other stent had experienced 3 ETO cycles. After the 3 day incubation, the stents were examined under Reflectance infrared spectroscopy, and it was confirmed that the coatings did not detach from the Zomaxx or the one-step stents.
It will be apparent to those skilled in the art that various modifications and variations can be made in the method and system of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention include modifications and variations that are within the scope of the appended claims and their equivalents.
|Cited Patent
|Filing date
|Publication date
|Nov 3, 1993
|Oct 18, 1994
|Cordis Corporation
|Biocompatible metal surfaces
|Aug 30, 2001
|Oct 29, 2002
|Estrogen Vascular Technology, Llc
|Apparatus and method for delivering compounds to a living organism
|Feb 13, 2001
|Oct 29, 2002
|Avantec Vascular Corporation
|Intravascular delivery of mycophenolic acid
|Nov 24, 1998
|Oct 21, 2003
|Morphoplant Gmbh
|Immobilizing mediator molecules via anchor molecules on metallic implant materials containing oxide layer
|Apr 26, 2002
|Feb 27, 2003
|Jianbing Chen
|Polymer-based, sustained release drug delivery system
|Apr 24, 2002
|Jul 3, 2003
|Shulze John E.
|Drug-delivery endovascular stent and method for treating restenosis
|Nov 7, 2003
|Sep 23, 2004
|Donald Verlee
|Prosthesis with multiple drugs applied separately by fluid jet application in discrete unmixed droplets
|Apr 18, 2000
|Oct 26, 2000
|Boston Scientific Limited
|Coating medical devices using air suspension
|Apr 28, 2000
|Nov 2, 2000
|Eidgenossisch Technische Hochschule Zurich
|Polyionic coatings in analytic and sensor devices
|May 30, 2000
|Jan 11, 2001
|Biocompatibles Limited
|Local drug delivery
|Jan 24, 2001
|Aug 9, 2001
|Zoucas Kirurgkonsult Ab
|Medical device
|Jan 11, 2002
|Jul 18, 2002
|Biocompatibles Uk Limited
|Drug delivery from stents
|Jul 8, 2002
|Feb 13, 2003
|Zoucas Kirurgkonsult Ab
|Heparin stent
|Feb 14, 2003
|Aug 21, 2003
|Cv Therapeutics, Inc.
|Polymer coating for medical devices
|Sep 15, 2003
|Mar 25, 2004
|Linvatec Corporation
|Drawn expanded stent
|Joung et al., "Estrogen release from metallic stent surface for the prevention of restenosis," J Control Release. Sep. 19, 2003;92(1-2):83-91.
|Lewis et al., "Analysis of a phosphorylcholine-based polymer coating on a coronary stent pre- and post-implantation," Biomaterials. Apr. 2002;23(7):1697-706.
|Lewis et al., "Crosslinkable coatings from phosphorylcholine-based polymers," Biomaterials. Jan. 2001;22(2):99-111.
|Lewis et al., "Phosphorylcholine-based polymer coatings for stent drug delivery," J Mater Sci Mater Med. Oct.-Dec. 2001;12(10-12):865-70.
|Lewis et al., "Phosphorylcholine-coated stents," J Long Term Eff Med Implants. 2002;12(4):231-50.
|Palmer et al., "Biological evaluation and drug delivery application of cationically modified phospholipid polymers," Biomaterials. Aug. 2004;25(19):4785-96.
|Swanson et al., "Human internal mammary artery organ culture model of coronary stenting: a novel investigation of smooth muscle cell response to drug-eluting stents," Clin Sci (Lond). Oct. 2002;103(4):347-53.
|Walter et al., "Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis," Circulation. Jul. 6, 2004;110(1):36-45. Epub Jun. 21, 2004.
|U.S. Classification
|427/2.25, 623/1.12, 623/901, 521/142, 623/23.58, 623/11.11, 424/422, 424/423, 623/1.15, 424/468, 427/2.24, 623/1.42, 623/900
|International Classification
|Cooperative Classification
|European Classification
|Aug 8, 2007
Owner name: ABBOTT LABORATORIES, ILLINOIS
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TARCHA, PETER J.;PECOSKY, DAVID;REEL/FRAME:019665/0120;SIGNING DATES FROM 20070801 TO 20070806
Owner name: ABBOTT LABORATORIES, ILLINOIS
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TARCHA, PETER J.;PECOSKY, DAVID;SIGNING DATES FROM 20070801 TO 20070806;REEL/FRAME:019665/0120
|May 26, 2015
|Fee payment
Year of fee payment: 4


text:
Target: Le député UMP Frédéric Lefebvre
Goal: Praise the success to no longer classify domestic animals as "furniture"
Recently, France's parliament voted in favor for no longer classifying domestic animals as "furniture" but as "living beings capable of sensitivity." This is a huge step in France to better protect animals and to seek harsher punishment for those who abuse or mistreat them. A previous ForceChange petition commended French legislators for working to reclassify domestic animals. The push for legislation was made possible by many animal rights groups and supporters, but French legislator Le député UMP Frédéric Lefebvre made notable progress by putting forth the legislation for a vote.
This battle has been going on for years, making this success even more notable. The code that classified them as furniture in a legal sense was first drafted in 1804, so it was clearly time for an update in the code. Animals were thought of as simply tools for agricultural purposes back then and did not take into account the welfare of domestic animals. The reason that the law took so long to change was due to concerns from farmers that this new law could hurt the agriculture business, although the legislation does not go so far as to extend to farming animals, unfortunately. The new legislation is a positive step forward and will change the mentalities of judges and prosecutors in France in favor of domestic animals.
Le député UMP Frédéric Lefebvre has made a positive impact in France by pushing so hard for this legislation to pass. Animals everywhere should be treated as "living beings capable of sensitivity" and not something similar to an armchair. Sign the petition below to thank Le député UMP Frédéric Lefebvre for his hard efforts to no longer classify domestic animals as "furniture."
Dear Monsieur Le député UMP Frédéric Lefebvre,
I would like to thank you for your significant efforts to push for legislation that will no longer classify domestic animals as furniture. This is important for the health and well-being of domestic animals in France, and the recent passing of this legislation makes greater protection of domestic animals a reality.
Please continue your efforts to make the world a better place for animals. While this is a huge step for France, more legislation could be enacted to further help animals, such as extending protection to farming animals or wild animals. Animals everywhere should be thought of as more than just furniture so that we can continue improving their lives. Thank you once again for making this legislation possible.
[Your Name Here]
Photo credit: Kaz via Pixabay


text:
- HubPages»
- HubPages Tutorials and Community
Hubbers Anonymous
HubPages Addict - I Need Hubbers Anonymous
Ahem. Hello, my name is Shirley and I'm a Hubaholic.
This is my first time voicing this in front of a group but I'm confident that I'm not alone in my affliction, that there are others out there who need a hubbervention. (new word - hubber + intervention)
If this hub can help just one hubber conquer the HubPages monkey, then my work will have been successful. (See, admitting the truth is helping already, I only used the word, 'hub' three times in one sentence)
Symptoms of Hub Addiction
You may be sitting there denying the truth about how strong the HP hold is on you. Believe me brothers and sisters of the hubs, you have to face it to conquer it.
Force yourself to look at the following list of warning signs and honestly reflect on whether or not they apply to you.
Benson is a doctor so listen up!
You May Be a Hubbaholic....
Warning Signs of Hubaholism
- The first thing you do upon rising is check your hubscore and comments
- You tell your spouse, "Not tonight honey, I've got a hub to finish"
- You leave family gatherings just to quickly check in at HubPages. Either you do this 18 times or you don't rejoin the others for 3 hours
- The Last Post forum thread is your idea of 'the good old days'
- You develop an alternate hub identity because of the Last Post forum thread (you know who you are and so do I!)
- Your hand trembles if the HP page load is slow
- You tell all your friends and family about the hubbers that you hang out with on the site. People who support your addiction become more and more important
- You spend a lot time thinking ahead to what your next 17 hubs could be about. It's vital never to run out, to be *gasp* hubless and risk the D.T.'s
- You only eat finger foods so you don't have to leave the computer. You've lost 36 lbs. but your cholesterol has quadrupled
- You feel stressed for time because you HAVE to get your hub done and published so you can hurry up and do the next one and the next, more, more, more! Pretty soon, you're spiralling out of control
- You start looking for ways to write more hubs faster, start hanging out in the forums and end up begging and pleading the prolific hubbers for their 'secrets'. Signs that you need a bigger, faster fix
- If you're writing 'hot' on a hub, you'll forgo eating, sleeping and working somewhere else to finish it in triumph
- You name your puppy or baby after another hubber
- You look for ways of working at home so you never have to sign out, in fact you're racking your brain trying to scheme up ways to make a living at hubbing
- When it comes to choosing whether to let your meal burn or finish your conversation with a fellow hub addict, the meal loses
- You often find that your legs are crossed or bouncing up and down because your bladder is about ready to burst, but you just want to finish up this hub first before going pee
- You take your laptop in the delivery room even though you're the one giving birth
- HubPages is named as the co-respondent in your divorce papers
This Could Be You!
One Hubber's Sad Story
A Tale of the Ugly Side of Hub Addiction
in Maestrowhit's own words...
* Page that linked to the quote has disappeared.
"I see that it is lunch time, so I get up from my PC and go to the kitchen to cook something. I place my food in the hot pan and wait for it to cook. I think to myself, "why wait here by the boring stove when I can go back to HubPages and finish that enthralling discussion I was in!" So I go back to my PC with every intention of getting right back after a few minutes to take my food off the hot stove. From the minute I type the first word, my internal clock gets all screwed up, and what seems like five minutes is actually fifteen minutes. I don't realize this until the scent of smoke reaches my nostrils. So be very careful! This has happened to me more than once. It could happen to you too!"
...and later, after reading Benson Yeung's professional advice
"Oh, crap! That reminds me.....MY TURKEY IS BURNING!"
B.T. Evilpants
How One Hubber Deals with the Shame
B.T. Evilpants recently went public to openly acknowledge not only that he suffers from hubaholism but also the fact that he hides one of the more common tell-tale signs.
"Happens all the time. That's why I keep plenty of gravy on hand, to smother things."
Practical Advice from a Pro
Hi Shirley. One way to save your marriage is to have one more computer in the house so that you can video-skype with your better half while you both hub along. Or better still, you both hub on the same topic at the hubber's hangout. Disclaimer: this remedy has not been approved by the FDA and carry no scrutinized scientific evidence on it.
- Benson Yeung, Surgeon and all around smart hubaholic
Editor's note: One out of one doctor that we consulted here on HubPages endorses the careful use of hubbing. In moderation, it's perfectly safe and not habit forming.
How to Kick the Habit & How I've Failed Miserably
Kicking the habit, that's why we're here isn't it? Well okay, maybe not. Let's face it, we don't want to stop, or at least I don't want to. I don't even need to, I can quit any time I want. I just don't want to, I'm not ready.
What was I thinking when I decided to write this hub? All I've suceeded in doing is relishing in my addiction. A giant step backwards, if you will. I don't have any tips on how to quit!
If any of you are stepping up to the hubplate to take the plunge into the sterile world of hubsobriety, well my hat's off to you and I wish you much luck and ask that you please not try to convert the rest of us. I think, that short of the end of the world as we know it, most of us won't kick. We experimented and got sucked into the underground world of seedy topics and comments stuffed in brown bags and read down dark alleys.
Just talking about all this Hubbers Anonymous stuff is making me antsy to start another hub. Withdrawal kicks in so fast!
To take liberty with some Brian Ferry lyrics, Hub is the drug I'm thinking of.
Other, More Serious Addictions
Join Us!
Come and be part of our nurturing writing community. Sign up for your own HubPages account and publish your work for others to see. You can even use your Hubs as sample clips when querying online publications. Publishers will be able gauge the caliber of your writing and you'll be making a bit of extra money at the same time. Can't beat it!
© 2008 Shirley Anderson
Welcome to the club fellow addict lol.....jimmy
The real question is, "Is every addiction a problem?" I mean, why would you want to kick the habit? :p
This is fantastic and I did leave Thanksgiving early so that I could publish and write, and I have burnt things as the hubis priority, yes I am addicted and it is a wonderful addiction!! I love it and thank you for writing iT!! Happy Thanksgiving and now I can grab a quick snack.:)
That's hysterical! You have plenty of support here :) I have lots of favourites amongst your warning signs, but the winner has to be naming your puppy or baby after another hubber. I have frequently checked my hubscore when there have been guests here. And I've always got about 10 hubs on the go, lest my hub supply should run dry...
Hi - I'd just like to say there is a really simple solution to the burnt dinner problem: a laptop- so you can hub in the kitchen! BTW as soon as we stopped camping and rented a flat guess what the 2nd thing we bought was: the first was a microwave, the 2nd - a laptop for my partner so he didn't get between me and the hubs!
Too funny, Shirley! I wondered if it was a little sad that I looked forward to Thanksgiving dinner ending so that I could get home and check my hub traffic. :D
I do NOT have a problem! I can quit any time I want! Really. Maybe I happen to like my food burned, and smothered in gravy.
Shirley I can't stop giggling. What a way to capture the intensity of hubbing. I love it. Stuff like this give ma a high. LOL. What a fix! hahaha. Keep them coming.:)
Hello, my name is Dineane, and I'm a Hubber...
I am reading this after just finishing our Thanksgiving dinner, so I guess it gives me away as Hubaholic. LOL! Your hub made smile, and I tell ya, I am very grateful for this community of diverse writers that keeps me entertained, informed and oftentimes inspired.
"And... hello, my name is Marie and I am a hubaholic, and proud of it! hehe"
Hello, my name is Daisy, and I'm in denial. LOL. Oh boy, I think I'm delirious now. Thanks Shirley...(starting to get groggy) will be ...back for more..:)
(jerks up) Huh? Say what? Oh...hehe.. (drops to sleep and dreams of the next hub she MUST write)
Hahahah yes dear Shirley. I was just in my "creative mood", thanks to you. I like to fool around with friends and use my acting ability to have fun. I do enjoy these exchanges with you. This type of session is really helpful for a Hubaholic like me. LOL. Do have a good rest. Godbless:)
You can say that again! LOL. See, this comment box has now turned into a chat service. hahahahaha. Now I know where to go for a fix:)
My name is Annie and I too am a Hubaholic - just love it - must admit that I have oversteamed vegetables, left meat on the oven a wee bit too long just so that I can check the score, hot hubs, laughs on hubs, & to see who is involved with whom in some convoluted issue ....it's all a bit of an addictive worry really, but oh so much fun! no cure I'm afraid...
Hi, Shirley!
If I count correctly, you list 18 Warning Signs of addiction. So if, say, a certain Hubber has only 11 out of 18, then I ... er... they, ummm, don't have a problem, right?
A ... friend of mine ... yeah, that's it ... a friend of mine wants to know.
And for myself, I gotta say, Great Hub!
I don't suffer from hubaholism, at all. I enjoy every second of it! I am a functioning hubaholic. And I never hub and drive!
Dear Shirley,
very smart and well-rehearsed use of ideas from the recent forum thread, another sign of severely diseased hubaholics. You should start drinking beer to kill off the slowest functioning brain cells. That's your only chance.
Now THAT sounds like the voice of wisdom! You should listen, Shirley. It would probably be a bad idea to question a doctor's advice. I would start with a Labatt's. In fact, I already did!
very intreresting
LOL, now that I was almost quitting hubpages you just ruin it :D
Oh well, I´m going to put my dinner into the oven... and now lets keep reading some hubs :D
Honestly, I try everyday to avoid coming here but it´s stronger than me :rolleyes:.
Sometimes you just have to quit quitting, funride. Sometimes what you need, is a little hair of the dog.
@ B.T. Evilpants - ... hair of the dog!? LOL I guess you´re right, I am now quitting quitting :D
@ Shirley - I would love to say it goes to heaven but in fact it goes up to a fire watcher tower. BTW, I took this photo myself with the camera on the ground. You can see it bigger here http://photos2.hi5.com/0053/884/217/XZ7Evo884217-0... , on the background you can see Obidos Lagoon which it´s not far from where I live ;)
It seems to me that there are many hub addicts 'round here. :) Wait. You may have left out a lot of others who still don't admit. :O
That was GREAT!!!!! I too am a Hubaholic...It's because I hang out here with all the people my mother warned me about
Hello, My names comp, and I too am a hubaholic! It seems, Shirley, like we are not alone and compared to my other addictions, this one, i can be proud of, and u2;) and Im so glad your an addict! :)
Hi Shirley!, i have been confused many times too! trying to find the real me!:/
Im working on a new avatar!!, i did think of comments that people have made relating to my original avatar! so i have placed a pic in pic, i was thinking of a pic, in pic in pic!
Watch this space..
Oh well, no more furry pants:(
I understand it all -- No Internet conenction is fast enough and I want a voice recognition program so I no longer must type.... And 5 computers so I can do multiple Hubs at once.
My technique is to limit my hub time to 10 or 15 minutes. Unfortunately, I do that at least 6-8 times a day. If my wrist watch had an internet connection and a keyboard, I'd think i died and went to heaven!
Think I'll pass on that one, thanks. I get a little scared, every time he goes down into that bunker. I heard barking down there, just yesterday.
I'm sorry to be avoiding you Shirley on this subject but I am in denial and am not ready to admit it yet. I'll be back later with an update!:)
Hilarious Hub :), I think we are mostly in the denial stage. Hubaholic is a great word.
I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubhaolic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic, I am not a hubaholic!!!!!
Glad I got that off my chest.
I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial, I am not in denial,
Hi Shirley, I dreamt I was in front of a computer writing a hub and woke up with my hand typing in the air. Gosh am I getting screwed up in the head? LOL Dr. Benson, help, I need an appointment! :) tee hee
I guess I just don't see what the addict gets out of HP. Hardley MONEY! At least with drugs you get high. Just a dabbler.
Very funny hub! I so relate! I used to be addicted to the computer, period. I was literally glued to it in every waking spare moment. Remember that commercial, 'it's 10 pm, do you know where your children are?', well, my kids definitely knew where mom was :)
I have to say, I have since weaned myself from having to sit in front of this thing, I can actually leave it for a day or even two at a time, without suffering withdrawals. However, when I do sit here, the first thing I do is check hubpages. It used to be eBay, and the good news is, this addiction doesn't cost a penny. So, I can justify my addiction to hubpages. It's saving me money :)
Hi Ripplemaker,
you don't need an appointment. You just need beer. If you really want to consult me. We both need the skype video running in the background of our hubbing. Still we will not have enough time for that. I suppose just the beer will do.
look out. If something doesn't cost you money, it usually causes a part, usually quite substantial, of your life.
Hi Shirley,
sorry that I have un-invitedly co-hosted your hub. You probably will understand and forgive this kind of obsessvie compulsive behavior in a fellow hub-aholic. I have really done well today, not signing in for 23 hours in a row and rightly deserve a pat on the shoulder.
Shirley, I used to feel that way. It was so bad that even if I had company, I had to have the computer on, and when I went visiting, I made sure to be near a computer. After all, I might miss finding my knight in shining armor, or miss the email that said I was the grand prize winner of $1,000,000. Hah! how mistaken I was. And how very pathetic LOL,,
You can do it though! Really!
LOL, it's not as awful as it seems Shirley
Benson, I'll give up part of my life for this, where else could I go and be entertained, be sociable and educated all at once? all from the privacy of my own home. I love it! :)
LOL Shirley, you're like a cat, just waiting to pounce! Is that another symptom?
My wife has taken my computer from me. But I'm not worried. I have another one stashed under the mattress and another in the garage. In a pinch there's always the computers at the library. Come home with a copy of "Spatial Relationships in Escher Paintings" and she's none the wiser.
Yes I was Shirley...I guess I do have symptoms....ok I'm slowly coming out of denial...are you watching me, by any chance? pounce
Shirley, this is priceless! I'm a hubaholic too, and I have suffered from all of the symptoms Benson has mentioned...except for constipation. I hesitate to mention this to other hubaholics because it's frightening to talk about, but my hubtivity has decreased over the past few days due to...intermittent loss of internet service!
Yes, it's true, and yesterday I lost internet totally. It was dead, and it was horrible. I broke out in a sweat, I got the shakes and became irritable, my hair stood out on end - all 2 feet of it, and I could of sworn I saw Jesus. I started plotting how to steal internet from some place else. Like maybe I could take my son's laptop and drive around till I could pick up on someone else's wireless signal, but he locked himself (and the laptop) in his room and told me to go take a nap or something. I had to take 4 naps. It was ugly, very ugly. ;)
Thanks for the chuckles Shirley! ;)
Shirley if you are still spying please go and check your mailbox. There is a surprise for you it is soooo beautiful and it is not from me. Wait till you see it. Go get it now. I know you are spying. GO to the mailbox NOW!
Fabulous hub Shirley--I like to think that I've conquered my addiction and that these days I am a social hubber--but perhaps I am just in denial :-) I don't have the physical signs--no insomnia or constipation and just what is a libido anyway???... and my Thanksgiving turkey didn't burn( but of course I didn't cook it) so I must be cured of my addiction, right??? ROTFL
Isn't it beautiful Shirley. Ya, I like that....Charlie's Angels! You are all on my Wall of Fame! LOVE IT! :)
BTW...it is after 10:00 pm and have not braked for dinner. Is this a sign? LOL I'm sooo hungry.
Hello Shirley and Dottie, it is simply adorable to witness your reaction to the surprise. I guess the surprise was partly caused by Hubaholism and Hublovinism?LOL.:)
Here is three of Charlie's Angels. Where is the other one! Where oh where can the ripplemaker be. Oh where oh where can she be!
(shirley, you don't mind me clicking on that ad under me do you? It said from the Boston area so had to check it out);) (if anyone wants to come down to Boston for the Rich Dad's education come on down Dec. 16 - 18. I'll put you's all up!
She's coming...she's back on line..wait for her....
Hahaha hello shirley, daisy and dottie!!! You like it? dottie, don't print it out yet, we would like to send you the one with the original photo size... hahahah that's funny you also thought of the name charlie's angels because that's what I told daisy. There is also another term I thought of -christmas angels! Hahahha
Dear Fellow Hubaholics, There is an urgent chat conference going on. Please wait for your turn and Shirley will get back to you soon.:)
Damn Rich Dad knocked me off line. I want my money back! Shirley it is after midnight I haven't had dinner yet! I'm going to die soon! I need water, Help Dr. Benson, Help!
I could not resist it. I saw an openning and had to do something. I couldn't just let it go like that. Please forgive me....
Charlie's angels is fine with me. LOL at least it will not be for xmas only. I like that. I would like to hug the 3 of you now at the same time. {(( hugs ))}
Good night all my sweet angels. I need food. Talk to you all tomorrow! Love you guys to pieces. Sweet dreams.
Good night and sweet dreams to Charlie's Angels. Shirley will be back online soon. Take care all:)
Dr. Benson, I don't drink beer. LOL Good night shirley and dottie. It's lunch time here so i might take a nap too...after all the typing. See you later daisy. :)
Spryte, Evil-Pants , Dayzeebee, Dottie, Hot Dork(age), JimmyJock, Maddie.
I swear i don't mean to be rude but I would love to name my future puppies with these really cute names. (",)
WOW!! Nice hub about something I didn't knew I had until I read the symptom's now I got to take appointment from our in house Doctor Benson. I wonder if my insurance would cover it. What is that smell?..... Dang there goes my curry on the stove ruining my kitchen stove..Got to attend to it and will back....hehe
Shirley, As I produced a serious hub several months back, but I am afraid by being subtle, trulynot wanting to be impolite by addressing such erudite persons with the fact that they have a 'problem', I chose to soft soup around that delicate issue and tried to reason with them, the writing was on the wall! https://hubpages.com/education/The-almost-Secret
Great hub
Hi Shirley - Noticed there was yet another one in the same vein :)
We're all in the same soup!
LOL, thank you Shirley. The good news is that I have lived to talk about my intermittent internet loss problem, and I haven't killed anyone. ;)
I hope Benson can invent a pill because I don't want you or any of us to be forced into a lobotomy. :) Actually, maybe we just need some tips on how to hide our addiction. Or good excuses. Or a doctor's note. ;)
I forgot to mention last night that I got so tickled over your editorial note..."One out of one doctors..." LOL! Good one! ;)
I maintain that I am not an addict! I simply need to keep coming back, because you just never know when some big-shot publisher is going to leave a comment, with a multi-million dollar job offer. You know what I mean?
LOVE this Hub! LOL - I see myself in just about every warning sign (not sure, if that is a good or bad thing), maybe it is just the addiction talking...I am certainly glad that there are so many of us...many who will not even admit they have a problem like B.T. up there (living in denial will not make it go away). I ADMIT IT! Fellow Hubbers are the only people that truly understand and I will gladly enable any fellow Hubber :)
I am not a hubaholic. I do not have a problem. My dearly beloved thinks I have. But she is mistaken. I often spend a day away, sometimes even two but then I have play comment catch up (like now for instance). I only publish around once a week, usually limited to hubmobs! So there!
Sixty, I have heard that being addicted to something, does not necessarily mean that you need it every day. It only means that you need it! You may be in the early stages of hubaholism, and the late stages of denial. The sooner you realize this, the easier it is to deal with! In the mean time, have a beer!
You can call me Mr furrypants again as i have added me under kitty!:)
Good Morning Ms. Hubaholic:
Just stopped by to see if my rehab appointment had been set by the doctor! Not yet I see. He's probably trying to beat out his 23 hr. hubber signon withdrawal symptoms.
LOL to Ashwin - like Shirley says, you got it bad boy but if your puppy needs a middle name it would be Dottie Marie!;)
And Shirley, we got a new kid on the block. Let us not fight over him ok. I won't pull your hair if you promise not to scratch out my eyes, please pinky swear!
Hello Shirley! Just dropping by to get a glimpse of "new addictions" for the day. LOL I'm off to work in a little while so you all take care.. :)
congratulations on turning a hundred, yet again. I don't mean your age of course.
Ok, so maybe I have a small problem. But it hasn't effected me at all. Really! Just ask my wife. Hey, wait a minute. I don't see her anywhere...and the closet is empty. Hmm...
Great hub. Hopefully i will soon be as good at writing hubs. Please visit my hubs and comment if you feel like it. Thanks
I joined hubpages two weeks ago and I am on here everyday, probably more than I need to be. Thank you for opening my eyes. I now understand whats going on.
Great hub.
Hello my name is Dorsi and I'm a hubaholic. I am here because I'm not giving up hubbing.LOL!!!!!!!!!
Hysterical hub- gotta love it!!!
Thumbs up!!
Guess you found a topic that really speaks to the people - my finger grew tired as I scrolled through the comments...though I am a relatively new hubber, I can see how one might develop an addiction. (Though isn't a hub addiction far better than a vain FB addiction?)Pointed question, I know.
I can't believe that it took so long to read this one. I love it. I have to admit that I suffer from it, too. I am horrible at it. My excuse is that I have to be polite to read the messages and since it is making money it needs my attention. I need some excuse.
Fantastic Hub! This is so true and so funny. Thanks for opening my eyes.