text:
A method of attenuating the symptoms of opioid withdrawal in a human or animal subject comprises administering to the subject an effective opioid withdrawal symptom attenuating amount of an inhibitor of nitric oxide synthase (NOS) for a period of time effective to attenuate such symptoms upon opioid withdrawal. NOS inhibitors useful in the present method include, for example, L-NG -nitroarginine, esters of L-NG -nitroarginine, L-NG -monomethylarginine, L-NG -benzylarginine, L-NG -aminoarginine, iminoethylornithine, and pharmaceutically acceptable salts thereof. These compounds can be used alone or in combination, in conjunction with conventional drugs, such as α2 -adrenoceptor agonists, mixed agonist-antagonist opioids, and NMDA antagonists, to attenuate the symptoms of opioid withdrawal. Effective doses of NOS inhibitors range from about 1 μg/kg/day to about 30 mg/kg/day, administered over the course of about 1 hour to about six days, followed by opioid withdrawal.
1. A method for attenuating the symptoms of opioid withdrawal in a human or animal subject, comprising administering to said subject an effective opioid withdrawal symptom attenuating amount of a nitric oxide synthase inhibitor for a period of time effective to attenuate said symptoms upon opioid withdrawal.
2. The method of claim 1, wherein said inhibitor is at least one selected from the group consisting of L-NG -nitroarginine, an ester of L-NG -nitroarginine, L-NG -monomethylarginine, L-NG -benzylarginine, L-NG -aminoarginine, L-N-iminoethylornithine, and a pharmaceutically acceptable salt thereof.
3. The method of claim 2, wherein said ester is selected from the group consisting of a benzyl ester and a methyl ester.
4. The method of claim 2, wherein said pharmaceutically acceptable salt is selected from the group consisting of a hydrochloride, a hydrobromide, a sulfate, a phosphate, a citrate, a fumarate, a maleate, an acetate, a sulfamidate, a lactate, a tartrate, a succinate, a methanesulfonate, an ethanesulfonate, a benzenesulfonate, and a p-toluenesulfonate.
5. The method of claim 1, wherein said administering is conducted orally, intramuscularly, subcutaneously, transdermally, intraperitoneally, by continuous infusion, or by intravenous drip.
6. The method of claim 1, wherein said nitric oxide synthase inhibitor is administered in a pharmaceutically acceptable carrier.
7. The method of claim 6, wherein said pharmaceutically acceptable carrier is selected from the group consisting of distilled water, saline, and acidified saline.
8. The method of claim 6, wherein said pharmaceutically acceptable carrier further comprises at least one of a safe dissolving aid, a buffering agent, or a stabilizer.
9. The method of claim 1, wherein said effective amount of said nitric oxide synthase inhibitor is in the range of from about 1 μg/kg/day to about 30 mg/kg/day.
10. The method of claim 1, wherein said effective amount of said nitric oxide synthase inhibitor is in the range of from about 1 mg/kg/day to about 25 mg/kg/day.
11. The method of claim 1, wherein said effective amount of said nitric oxide synthase inhibitor is in the range of from about 3 mg/kg/day to about 15 mg/kg/day.
12. The method of claim 1, wherein said effective amount is administered in a single dose, or in two to three smaller doses over the course of a 24 hour period.
13. The method of claim 1, wherein said effective period of time is from about 1 hour to about six days.
14. The method of claim 1, wherein said opioid withdrawal is conducted after about two days.
15. The method of claim 1, wherein said opioid withdrawal is conducted after about 1 hour to about six days.
1. Field of the Invention
The present invention relates to the use of inhibitors of nitric oxide synthase (NOS) for the attenuation of the opioid withdrawal syndrome. It is applicable to human drug addicts who are dependent on drugs like heroin, or who have been maintained for a period of time on methadone, and wish to be completely free of drugs.
2. Description of Related Art
Two major classes of drugs are presently used to attenuate the opioid withdrawal syndrome. The first class includes ∝2 -adrenoceptor agonists, of which clonidine is the most commonly used (J. H. Jaffe, "Drug addiction and drug abuse," The Pharmacological Basis of Therapeutics, A. G. Gilman et al., eds., Pergamon Press, New York, 1991, pp. 522-573). ∝2 -Adrenoceptor agonists presumably act on the same neurons, but at a different receptor, as those affected by opioids (Aghajanian, G. K., "The neurobiology of opiate withdrawal: receptors, second messengers, and ion channels," Psychiatry Letter III:57-60, 1985). Clonidine is an effective attenuator of the opioid withdrawal syndrome. The major problem with its use, however, is that it lowers blood pressure. Therefore, its effectiveness is limited by the susceptibility of the patient to this effect. Another drug currently being tested for the treatment of opioid withdrawal is the mixed agonist-antagonist opioid buprenorphine (Mello et al., "Buprenorphine effects on human heroin self-administration." J. Pharmacol. Exp. Ther., 223:30-39, 1982). Presumably, mixed agonist-antagonists work to attenuate the withdrawal syndrome at the opioid receptor itself. This drug is also effective, but suffers from potential abuse liability because of its opioid agonist properties (Fudala et al., "Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal," Clin. Pharmacol. and Ther., 47:525-534, 1990).
Data from animal experiments have linked opioid withdrawal and activation of glutamatergic neurotransmission (Rasmussen et al., "Withdrawal-induced activation of locus coeruleus neurons in opiate-dependent rats: attenuation by lesions of the nucleus paragigantocellularis," Brain Research 505:346-350, 1989; Rasmussen et al., "NMDA antagonists suppress behaviors but not norepinephrine turnover or locus coeruleus unit activity induced by opiate withdrawal," Eur. J. Pharmacol. 197:9-16, 1991). Recently, Trujillo et al. ("Inhibition of Morphine Tolerance and Dependence by the NMDA Receptor Antagonist MK-801," Science 251:85-87, 1991) reported that inhibition of N-methyl-D-aspartate (NMDA)-type glutamate receptor with MK-801 effectively attenuates jumping behavior observed in opioid-dependent rats during withdrawal, suggesting a new intervention strategy, i.e., inhibition of the NMDA neurotransmission. The class of drugs to which MK-801 belongs blocks the NMDA-gated ionic channel. Drugs of this class, which includes phencyclidine, have abuse liability, and produce untoward side effects such as hallucinations and bizarre behavior. Moreover, they produce neurotoxicity, which limits their use as pharmaceuticals (Olney et al., "Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs," Science 244:1360-1362, 1989).
New information concerning NMDA-type glutamatergic neurotransmission indicates that some of the consequences of activation of this receptor are mediated through nitric oxide, which acts as an intercellular messenger (Garthwaite, J., Trends in Neuroscience 14:60-67, 1991). Inhibition of the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), through compounds such as NG -nitroarginine (nitroarginine) has profound inhibitory effects on several consequences of NMDA receptor activation. For example. NG -nitroarginine blocks neurotoxicity and stimulation of cyclic GMP production in cultured neurons (Dawson et al., "Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures," Proc. Natl. Acad. Sci. USA 88: 6368-6371, 1991). Thus, inhibition of nitric oxide synthase appears to provide a means to antagonize the effects of NMDA receptor activation while bypassing an action on the NMDA-gated ion channel (i.e., dizocilpine-like action). Accordingly, this lead the present inventors to test the effects of inhibition of NOS with nitroarginine on opioid withdrawal.
The approach to attenuation of the opioid withdrawal syndrome encompassed by the present invention is radically different from any approach in current clinical use. The site of intervention is not the opioid receptor (buprenorphine), or even a receptor which is colocalized with the opioid receptor (clonidine).
The present approach also differs substantially from that cited in previous reports on interference with the NMDA receptor. By interfering with NMDA-type glutamatergic neurotransmission at a part of the pathway that is remote from the receptor, the potential for abuse liability should be substantially reduced, as should the untoward psychiatric manifestations and toxicity of drugs like MK-801.
The present novel approach possesses the following advantages:
(a) Animals receiving nitroarginine do not exhibit lower blood pressure. In fact, treatment with nitroarginine produces moderate elevations in blood pressure.
(b) Data, infra, disclose that nitroarginine effectively reduces several signs of opioid withdrawal (wet dog shakes, diarrhea, abnormal posturing) without affecting locomotor activity (FIG. 3). Clonidine produces similar attenuation of wet dog shakes, diarrhea and abnormal posturing, but increases other withdrawal signs substantially (locomotor activity and jumping).
Accordingly, it is an object of the present invention to provide a method for attenuating the symptoms of opioid withdrawal in a human or animal subject, comprising administering to said subject an effective opioid withdrawal symptom attenuating amount of a nitric oxide synthase inhibitor for a period of time effective to attenuate said symptoms upon opioid withdrawal.
Further scope of the applicability of the present invention will become apparent from the detailed description and drawings provided below. However, it should be understood that the detailed description and specific examples, although indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
The above and other objects, features, and advantages of the present invention will be better understood from the following detailed descriptions taken in conjunction with the accompanying drawings, all of which are given by way of illustration only, and are not limitative of the present invention, in which:
FIG. 1 shows nitroarginine dose response effects on withdrawal signs in rats;
FIG. 2 shows nitroarginine dose response effects on weight loss due to diarrhea in rats;
FIG. 3 shows the lack of effect of nitroarginine on locomotor activity in rats;
FIG. 4 shows the time course of the effect of nitroarginine on wet dog shakes in rats:
FIG. 5 shows the time course of the effect of nitroarginine on weight loss due to diarrhea in rats;
FIG. 6 shows the time course of the effect of nitroarginine on escape jumps for the first five minutes after naloxone administration in rats.
The entire contents of each of the references cited in the present specification are herein incorporated by reference in their entirety.
The following detailed description of the invention is provided to aid those skilled in the art in practicing the present invention. Even so, the following detailed description should not be construed to unduly limit the present invention, as modifications and variations in the embodiments herein discussed may be made by those of ordinary skill in the art without departing from the spirit or scope of the present inventive discovery.
Morphine pellets were implanted under halothane anesthesia in four month old Fisher-344 rats on a schedule that has been previously shown to produce morphine dependence (Kimes et al., "Glucose utilization in the rat brain during chronic morphine treatment and naloxone-precipitated morphine withdrawal," J. Pharmacol. Exp. Ther 248:538-545, 1989). Rats received one pellet (University of North Carolina School of Pharmacy, Drug Products Program, Chapel Hill, N.C.) containing 75 mg morphine on the first treatment day, and two pellets 3 days later. As nitroarginine has been shown to inhibit cerebral NOS maximally after 4 days of treatment (Dwyer et al., "Nitric oxide synthase: irreversible by L-NG -nitroarginine," Biochemical and Biophysical Research Communications 176 1136-1141, 1991), it was administered for 4 days in the first experiment. Rats were given nitroarginine by intraperitoneal injection twice a day for 4 days, starting on the day the second set of morphine pellets were implanted. Opioid withdrawal was initiated on the 8th day by an injection of 0.5 mg/kg naloxone. The rats were placed in a plexiglas� observation chamber, and their behavior was observed for 15 min. Opioid withdrawal signs in animals receiving one of three doses of nitroarginine (1 mg/kg, 3 mg/kg and 7.5 mg/kg) were compared to opioid withdrawal signs in animals receiving no nitroarginine. Nitroarginine reduced several signs of opioid withdrawal, such as wet dog shakes and weight loss, in a dose-responsive fashion (FIG. 1 and FIG. 2). As shown in FIG. 3, nitroarginine had no effect on locomotor activity.
To establish the most effective timing of administration of nitroarginine on opioid withdrawal, nitroarginine (7.5 mg/kg) was administered via two additional treatment regimens: by continuous infusion via Alzet� pumps starting at the time of the first morphine pellet implantation, and by a single injection 1 hour before opioid withdrawal was precipitated by the opioid antagonist, naloxone. The data show that nitroarginine is effective in reducing some of the opioid withdrawal symptoms irrespective of the administration schedule (FIG. 4). However, the greatest number of symptoms affected and the magnitude of the effect was usually greatest when the drug was administered for 4 days before the precipitated withdrawal (FIG. 5 and FIG. 6).
As disclosed by the data discussed supra, inhibition of the production of nitric oxide by inhibiting its synthetic enzyme reduces the severity of the opioid withdrawal syndrome in rats. These findings further suggest that inhibiting the production of nitric oxide in human opioid addicts would be an effective treatment strategy.
The nitric oxide synthase inhibitors useful in the present method include, as noted above, L-NG -nitroarginine. Also useful in the present method are esters of L-NG -nitroarginine, such as the benzyl and methyl esters, L-NG -monomethylarginine, L-NG -benzylarginine, L-NG -aminoarginine, and L-N-iminoethylornithine. Other NOS inhibitors which can be used in the present invention can be ascertained by routine methods well within the ordinary skill of the art. For example, Dwyer et al. (Biochem. Biophys. Res. Commun. 176:1136-41, 1991) provides guidance as to screening methods for determining the NOS-inhibitory properties of various compounds.
The NOS inhibitors useful in the present invention can be used alone, in combination with one another, or in combinations with other classes of drugs useful in attenuating the opioid withdrawal syndrome. The latter include α2 -adrenoceptor agonists, of which clonidine is an example; mixed agonist-antagonist opioids, such as buprenorphine; and NMDA antagonists, which block the NMDA-gated ionic channel, such as MK-801 and phencyclidine. When used in combination with these other classes of drugs, the NOS inhibitors of the present invention can serve to attenuate the undesirable side effects of these other drugs, described supra.
In the above-noted applications, the NOS inhibitors of the present invention can be used in the form of their pharmaceutically acceptable salts. These include acid addition salts formed with organic and inorganic acids, such as, for example, hydrochlorides, hydrobromides, sulfates, lactates, phosphates, citrates, fumarates, maleates, acetates, sulfamidates, lactates, tartrates, succinates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, etc.
While the nitric oxide synthase inhibitors of the present invention can be administered by intraperitoneal injection or by continuous infusion, another method of administration is by intravenous drip. Nitroarginine, for example, must be dissolved in acidified saline (pH 1.8). Administration by intravenous drip is suggested because this is the recommended method for administration of other relatively insoluble drugs, e.g., acyclovir, in which the pH of the administered drug would be too acidic or too basic to administer by intramuscular injection. Other pharmaceutically acceptable carriers and injection agents useful in the present invention, depending upon the specific NOS inhibitor(s) and other drugs employed, include, for example, distilled water, saline, etc., and further safe dissolving aids, buffering agents, stabilizers, etc., may be included as well.
Suggested doses of NOS inhibitors for the attenuation of symptoms of the opioid withdrawal syndrome in humans fall within the range of from about 1 μg/kg/day to about 30 mg/kg/day, more preferably from about 1 mg/kg/day to about 25 mg/kg/day, and most preferably from about 3 mg/kg/day to about 15 mg/kg/day. These doses may be given in a single administration via the methods described above, or in two to three doses per day over a 24 hour time period.
With respect to the time course of administration, the nitric oxide synthase inhibitor, or combinations thereof, can be administered orally, intramuscularly, subcutaneously, transdermally, intravenously, or otherwise for about one hour to about two days. During this period, the subject can be maintained on a dose of an opioid sufficient to inhibit spontaneous withdrawal. After a period of about 1 hour to about two days, opioid administration can be discontinued. In either case, administration of NOS inhibitor(s) would be continued for at least about an additional 2-4 days in order to attenuate symptoms associated with eventual withdrawal. Thus, the effective period for administration of the NOS inhibitor ranges from about one hour to about six days. As nitroarginine irreversibly inhibits NOS (Dwyer et al., Biochem. Biophys. Res. Commun. 176:1136-41, 1991), enzyme synthesis is necessary for NOS levels to return to normal after discontinuation of inhibitor treatment. This need for enzyme synthesis would extend the effectiveness of the drug beyond the point at which the drug is discontinued.
The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.
Non-Patent Citations
Referenced by
Legal Events
Original Image


text:
A123 said Sunday that the terms of the deal will see Wanxiang acquire its automotive, grid and commercial business assets, including all technology, products, customer contracts and U.S. facilities in Michigan, Massachusetts and Missouri. It will also get A123's cathode powder manufacturing operations in China and its equity interest in Shanghai Advanced Traction Battery Systems Co., A123's joint venture with Shanghai Automotive.
Excluded from the agreement is A123's Ann Arbor, Mich.-based government business, including all U.S. military contracts, which would be acquired for $2.25 million by Navitas Systems, a company that makes energy storage products for commercial, industrial and government agencies.
""We think we have structured this transaction to address potential national security concerns expressed during the review of our previous investment agreement with Wanxiang announced in August, as well as to address concerns raised by the Department of Energy," said A123 CEO Dave Vieau in a statement. "We believe this transaction balances those risks with A123's obligation to act in the best interest of our creditors."
If the deals are approved by the court, the shares will be worthless. That's because proceeds from the sale of the two parts of A123 would be less than the company owes its creditors.
Based in Chicago, Wanxiang America has been in the automotive and industrial markets in the U.S. since 1994 and currently has more than 3,000 U.S. employees. It is a subsidiary of Wanxiang Group, China's largest automotive components manufacturer and one of China's largest non-state-owned companies.
"We plan to build on the engineering and manufacturing capabilities that A123 has established in the U.S. and we are committed to making the long-term investments necessary for A123 to be successful," said Pin Ni, president of Wanxiang America.

subset: commoncrawl


text:
Marcellus MPhotographer Male Aurora, Colorado, US
My Website: Me on InstagramMy MM URL: http://www.modelmayhem.com/marcmabry
Mayhem # 364517
About Me
(Re-activated/Returned 03/16/15)
I'm back after a long break from model photography. Thank you for taking the time to look at my portfolio.
I am here for the purpose of perfecting my craft, and networking with creative professionals and artistic kindred.
In the process of re-shooting my e n t i r e portfolio, I am actively seeking models in the Denver area with a unique look.
The work in my portfolio is dated, but in time that will change.
I have a limited, but recurring need for—models (male and female), makeup artists, hair and wardrobe stylists for selective testing. Please check the "Casting Notice" listings if you are interested and meet the casting criteria. Thank you for reading my profile and viewing my portfolio.
Loading Content


text:
App doesn't run on device if LWUIT is obfuscated
I have just set up a demo app that basically puts a form on the screen and writes Hello World. I have written an Ant script that compiles and builds and packages and it all works fine on a real device. As soon as I obfuscate using Proguard (tried version 4.0 and 4.3) the app doesn't work. The device just reports an exception when starting. I am using Antenna and therefore the wtkobfuscate task.
Any ideas how I can obfuscate and still get the app to run on the device?


text:
Fact: Free scholarships for mothers can give you $10,000 to pay for your tuition.
To tap into the Obama moms college money fund you need to be a parent raising your children in a single parent environment, and you must have a desire to go to college and make something of yourself. Money arrives in the form of a grant, which means you will not be asked to pay this money back, you can study in peace and feel good knowing you are improving the lives of yourself and your children.
Fact: For The Pell Grant, funds are offered from the state directly, and from non profit organizations supported by the state can give you an additional $10,000.
When you are in school on the Obama grants for college program your fellow students will not know that you did not pay for the schooling yourself so there is no need to feel ashamed or feel as if you do not fit in.
These programs allow you to attend school full time, support your family emotionally and physically while studying full time at home and at school. There are usually enough funds to allow the parent to stay home with their children in the evening rather than needing to get a child care provider and going to work a full or part time job while in school. You will be able to focus all of your energy on learning and raising your family rather than rising enough money to pay your rent.
## Just click the link below to get started!
There is no reason to spend your own money for college.
$1000's of dollars has been set aside for you.
You never have to pay this money back as it falls into the same category as a grant.


text:
Star Trek A To Z
View Single Post
April 25 2012, 09:07 PM
Fleet Admiral
Location: The Warped Sector of the Demented Quadrant
Re: Star Trek A To Z
A is for Absent Friends, we toast them
B is for Bounty, HMS
C is for Captain J.T. Esteban of the science vessel USS Grissom
D is for Doctor David Marcus. Kirk's son. Killed by Kruge and left behind to disintergrate on the Genesis Planet when it exploded.
E is for Enterprise, USS, NCC 1701. blown to smithereens.
F is for Fedewation Battlecwuiser
G is for Genesis planet
H is for Harry Morrow, the admiral and Starfleet Chief of Staff
I is for Illogical. Perhaps how Dr. McCoy found several of his actions to be over the course of this film.
J is for Jim. Your name is Jim.
K is for Kruge. Kirk. has had. Enough of. HIM!
L is for Lexorin, for when you're suffering from a Vulcan mind-meld
M is for McCoy. Leonard H. Son of David.
"Human instinct is pretty strong. You can't expect us to change overnight."
-Jonathan Archer, 2151
View Public Profile
Send a private message to cooleddie74
Find More Posts by cooleddie74


text:
Standard Delivery: Dispatched in 1 business day(s)
_ [ 2355 x 24 Month 3051 x 18 Month
EMI Details
100% Authentic Brands
Product Covered Under Trustpay
TrustPay protects customers with a 100% moneyback guarantee if there is an issue with product quality, size or delivery
Seller Endorsed by brand for trusted and genuine product always
Built for speed
Get things done fast with the amazing Samsung NP350V5C-S06IN. Packed to the hilt with features the laptop is an apt answer to all your family requirements. The laptop has the latest Intel Core i7 Processor 3610QM running at 2.3GHz clock speed with 6MB L3 Cache to ensure that you get the best out of your laptop. It is enhanced by the cutting edge 8GB DDR3 RAM to allow you to multitask at your heart's content. The 1TB SATA hard disk allows you to store all your documents, images music and videos with space for even some more. The laptop comes with Genuine Windows 7 Home Premium (64-Bit) pre-installed so you can start working from the get-go!
Fully expandable ports
Rapidly exchange data with any external device at up to 5 Gbps using the latest USB 3.0 port that to give you the fastest data transfer speeds with compatible USB hard disks and USB thumb drives. The inclusion of an HDMI port and 15-pin DSub VGA Port ensures that you can take your laptop experience to the big screen like a separate computer monitor or a HDTV, even while you are playing games or watching movies. The connectivity is taken care by the in-built Bluetooth and Wi-Fi conforming to IEEE 802.11 b/g/n protocol standards. The laptop also has an Ethernet jack to connect to your home or office network without any hassles.
Anti-reflective screen
The anti-reflective screen allows you the brightest boldest and most vivid display with realistic colour representation even in bright sunlight. The screen is matte screen has no mirror effect, minimizing glare from bright light so you can take the laptop outdoors without any difficulty.
The key to easier use
The high quality keyboard with well-spaced keys makes typing a breeze, ensuring that you spend more time in a creative manner and less time correcting errors. Like a full-fledged desktop keyboard, the Samsung NP350V5C-S06IN has a numeric keypad to make number-crunching a cinch!
Optimised image quality
Samsung's innovative Image Enhanced Engine software improves image reproduction with vivid colours, sharp textures, crystal clear fonts and exqd>
Ask your Question :
Question Type :
Nick Name :
Your Question :
Question Type :
Nick Name :
Cool! Your question has been submitted.
Our masterminds are working on getting an answer. We will send you an email about it within 48 hours.POST A NEW QUESTION
Error While Submitting the Question. Please Try AgainTry Again
Displaying questions


text:
Code Oregon will offer free coding lessons to teach prospective employees how to develop software apps.
The Portland software maker expects to use the funds to hire more workers.
The Corvallis-based company raised $1.45 million from the Oregon Angel Fund for new semiconductor production technology.
FileString secured $1.9 million from 23 different angel investors; the majority of the capital comes from the Bay area.
The web designer will work in the Portland Development Commission's offices until it moves into a larger space in six months.


text:
Hear it First!
New issues, new real wedding features, new ideas and new inspiration delivered to your email.
Inside: Weddings across Colorado
what's new
Laura & John | September 6th | Colorado Springs, Colorado From the bride: Our wedding style is best described as "Rustic Elegant." I am a down-to-earth, outdoorsy girl, who ...
real weddings
inspiring details


text:
By Marlene Y. Satter |
January 26, 2012
This week in new hires, Putnam Investments welcomed Charlotte Walsh and Greg Weissman, Michael Belluomini was promoted at Securities America, and John Kim and Chris Blunt took new positions at New York Life.
By Marlene Y. Satter |
January 19, 2012
This week in new hires, Jane A. Norberg joined the SEC as deputy chief of the Whistleblower Office; Gregory J. Fleming was elected to FINRA's board of directors; Mike Anderson went to Securities America; and Dan Dorfman joined Trim Tabs Money Blog as a columnist.
LPL's white paper, Success Without Limits, will help you understand the various options and considerations for choosing the right partner.
Look behind the curtain and see how our fixed-income experts determine which municipals offer the greatest potential. With this proven approach to effective muni selection,...
Our research shows that two screens have helped achieve better outcomes - low expenses and high manager ownership. Funds sharing these two characteristics have tended...
Jul 09, 2015
In this session we'll discuss whether or not factor investing is truly active management, and how to define and test whether a factor exists.
Jun 30, 2015
Join ThinkAdvisor & Well Fargo in this webcast to learn a dynamic four criteria approach and how to gain portfolio flexibility.
Jun 09, 2015
Join ThinkAdvisor for this live, interactive webcast and hear from the winners of the 2015 SMA Mangers of the Year on impact investing strategies and...
© 2015 ThinkAdvisor. A Summit Professional Networks Website, A division of ALM Media, LLC. All Rights reserved.
Advertisement. Closing in 15 seconds.


text:
The Smurfs Puzzle Game. The game contains 50 levels with beautiful images from The Smurfs movie. Drag the pieces to the right place to create the image. Use pick button to preview the original image. Completed levels will be unlocked in gallery to install wallpaper or to save to SD. Try to complete all levels, the further you go the harder it gets.
Itâs up to you to build a new village for the Smurfs to call home.PLEASE NOTE: Smurfs' Village is free to play, but charges real money for additional in-app content.------------------------ Itâs snowing in Smurfsâ Village! Play a new holiday quest and decorate your village with seasonal cheer. ⢠Weâve added snow to the village and a free land expansion that unlocks around level 26! ⢠Play a new holiday quest staring Papa Smurf, Smurfette, Brainy, and
In the game you play as a little gnome who jumps and runs through the forest. In the game, our little leprechaun may carry different items. And collect all the bonuses that appear in your way. The game has many different levels, so you will not be bored with the change of environment. Have a nice spending time with our beautiful and good game.
You control a Smurf who must venture into the forest to rescue his fellow Smurfs that are being held captive by Gargamel. Along the way, Smurf can collect bonus items such as sarsaparilla leaves to increase his life count and raspberries to replenish his energy. Each section of the forest has its own set of dangers that Smurf must be careful to avoid. In the Super Nintendo and Sega Mega Drive versions, you must also at the beginning of the game make your way through the Smurf Village. Collecting stars in the Super Nintendo and Mega Drive versions will allow you to unlock bonus screens where Smurf can collect items to increase health and lives.
Far, far away, in a little mushroom village, live a group of little blue pixies in short trousers and white bonnets called The Smurfs. Only as tall as three apples, they speak in Smurf, a language that only they understand. The Smurfs are carefree, peaceful creatures that live in harmony with nature. But they have a nasty habit of wanting to act like man, which causes them 1,001 problems.


text:
David Linthicum offers three common errors made in adopting cloud services. Not planning for compliance, governance and security is one of them, and automatically selecting Amazon Web Services without considering any other cloud providers is another. He also advises users to be careful in choosing which applications and data to move to the cloud.
Full Story:InfoWorld


text:
Nominations for the 7th Annual Shorty Awards are now closed. All finalists have been announced. You can view
them by clicking on categories below.
Anyone can create a new Shorty Awards category by tweeting a nomination with a new
hashtag. There are over 4,015 user-generated categories.
Nominations for Brands & Organizations are now closed. All finalists will be announced soon. Official
categories are listed below.
Destroy the image and you will break the enemy. [Zero Hedge and Keiser Financial Wars] Visual Parody, Satire and Editorial
Voting in the Shorty Awards is currently closed. Check back soon!
Depends on the time of day
Guitars, computers, books, music, cameras, ideas, women
Zero Hedge
That it is another Facebook


text: Listeners Profiles Everyone (35) Profiles matching: Loving One Direction Everyone Mikay88888 Hometown: 1dland School: one direction school Employer: Loving one direction Stations: Ed Sheeran Radio, Lady Gaga Radio, Wrecking Ball Radio, Michael Jackson Radio sheilasanti206 Hometown: none of your business School: don't need to know lol Employer: loving one direction Stations: Banda Los Recoditos Radio, Reik Radio, Luis Enrique Radio, Los Panchos Radio Jasmine horan ^__^ Employer: Loving one direction Stations: The Neighbourhood Radio, Eminem Radio, Prince Royce Radio, Ed Sheeran Radio Jennifer Martinez Employer: loving One Direction!! Stations: Little Mix Radio, Keri Hilson Radio, 2 Chainz Radio, Miguel Radio Selena Herrera Hometown: Muskegon School: Oakridge Employer: loving one direction Stations: Zendaya Radio, Classical for Studying Radio, Michael Buble (Holiday) Radio, Katy Perry Radio Midnight Memories❤ Hometown: Direction Land;) School: ??Directioner?? Employer: ??Loving One Direction?? Stations: Ellie Goulding Radio, Lorde Radio, Pop Hits Radio, Noel Torres Radio Angie Blanchard Hometown: One direction town School: One direction high Employer: Loving one direction for life Stations: Rap 2014 Radio, Today's R&B and Hip Hop Hits Radio, Josh Gad Radio, Kristen Bell & Santino Fontana Radio Mrs.horan Hometown: carson School: carnegie ms Employer: loving one direction and justin bieber Stations: The Rolling Stones Radio, Little Peggy March Radio, The Temptations Radio, The Shirelles Radio Directioner for life Hometown: Lorence, Kansas School: Del Norte High School Employer: loving one direction Stations: Ciara Radio, Sabrina Carpenter Radio, Rich Homie Quan Radio, Cher Lloyd Radio WattPad; Tropical_Niall Hometown: On Earth With One Direction School: One Direction University Employer: Loving One Direction Stations: Olly Murs Radio, Hozier Radio, OneRepublic Radio, Coldplay Radio Show more