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In response to growing concern over the reliability and pricing of power, the
national commercial real estate firm of Julien J. Studley Inc., headquartered
in New York City, has developed a study on electric power in the United States.
The 32-page report, National Outlook on Power: Supply, Demand & Economic
Risk, provides a detailed analysis of electric power in 12 U.S. markets while
offering solutions for tenants seeking to protect themselves from outages and
price spikes.
Economic growth in the United States during the past decade has pushed consumption
of electricity to new heights. At the same time, the development of new generation
plants and transmissions systems has not kept pace, creating the potential for
future outages and price spikes devastating to businesses and prospects focused
on future growth. Notes CEO and Chairman Julien J. Studley, "Many national
corporations have already begun to examine power when contemplating a move."
The report includes an industry overview and sections on deregulation, price
volatility, reliability, technology, tenant savings solutions, strategies for
the future, a focus on selected U.S. markets, and more. For more information,
call (212) 326-1000 or visit (www.studley.com).
France Designs for Waste Management
What can be done with 31 million metric tons of waste generated every year by
building sites in France, at a moment when the demolition of 15,000 low-rent
housing units is planned for the country in the year 2003? According to the
French Technology Press Office Inc., based in Chicago, the risks and rewards
of sustainable development and the toughening of European legislation will progressively
cause manufacturers to recycle as much waste as possible and to limit the amount
that is dumped.
For this purpose, the CSTB (French Research Center for Building and Construction)
has developed an overall approach to waste management, ranging from the design
of construction products to demolition operations. It has two objectives:
The CSTB is evaluating the overall environmental performance of construction
products using Equity 2 software as a life-cycle analysis tool. It makes it
possible to evaluate ways to reduce the amount of waste generated by a product,
depending on the execution process, the type of maintenance, or building demolition
involved. The GRADE 2 software program currently under development makes it
possible to organize improvement and deconstruction sites by predicting procedures
and materials required to manage waste, hygiene and safety measures to apply
to a site, and ways to limit pollutant emissions and nuisances. To help manufacturers
identify a waste recycling activity, CSTB has also designed a "Recycling
Diagnosis," which makes it possible to estimate the technical, economic,
and environmental feasibility of any raw process that uses secondary raw materials
into construction products.
Interested in more information? Contact the French Technology Press Office at
(312) 222-1235; Fax (312) 222-1237.
Equity Office Properties Trust, the nation's largest publicly held office building
owner and manager has reached an agreement with Atlanta-based FacilityPro, a
builder and operator of private procurement marketplaces for the real estate
industry. By implementing FacilityPro's procurement marketplace, Equity Office
expects to streamline the purchasing process for its maintenance, repair, and
operations (MRO) products.
Nashville-based MagneTek Lighting Products, a leading manufacturer of electronic
and magnetic ballasts, recently announced its name change to Universal Lighting
Technologies. For energy-saving solutions, visit the company website (www.universalballast.
Recently, Milwaukee-headquartered Johnson Controls Inc. launched its e-business
portal solution to the U.S. real estate market. Called "Bosmart,"
the portal design integrates reporting tools to create a platform where a corporate
real estate team and the outsourcing partner can work more collaboratively.
Visit the Johnson Controls' website (www.johnsoncontrols.com).
What's your news? Let me know (email@example.com).
Visit our website today to learn about the design flexibility of a Morton building and the endless possibilities of partnering with our designBUILD team.
Wood construction is both cost and energy efficient. Check out Morton Buildings and our designBUILD team online today to discover all the benefits of post-frame construction.
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We Can Help You Reduce Energy by 30%
Our mission is to help our customers manage their buildings' energy costs, improve reliability, and enhance performance while having a positive impact on the environment.
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PROSOCO's R-GUARD FastFlash® the air & water barrier system used on the Bullitt Center, the world's greenest commercial building.
Dorlen products has three main product lines: Water Alert, Water Alert Sensor Cable and Ceiling Guard. Catalogs, Specifications and Pricing are available in .pdf form at our website.
Spot Coolers commercial portable heating & cooling. Nationwide Emergency service 24/7. Your source for portable air conditioning rentals and sales.
Need portable cooling for data centers, offices & more? Atlas Sales & Rentals is on call 24/7 from locations nationwide. Fast service, competitive prices.
DSX Access Systems – An industry leader in the design and sales of integrated access control products from single-door to enterprise-wide systems. www.dsxinc.com
Tremco Roofing and Building Maintenance is a leading supplier of sustainable roofing systems and services to help improve roof lifecycles and lower costs.
Cree Lighting is the leading innovator of LED chips, components and lighting systems. Discover a new world of cost-efficient LED lighting innovation at www.cree.com/lighting.
Yaskawa's Z1000 variable frequency drive is perfect for building automation applications that require reliable motor control.
The Amprobe LT-10 Lamp Tester takes the guess work out of troubleshooting fluorescent lighting; test bulbs, pins & voltage with one pocket-sized tool.
The BUILDINGS brand serves commercial building owners and facilities management professionals for commercial real estate. BUILDINGS brand offers its audience of commercial building owners and facilities management professionals information on the development, construction, modernization, management and operations of commercial buildings as well as the products and services needed to support such commercial buildings and facilities management. With the information we offer, we help facilities management professionals make smarter decisions for commercial buildings.
BUILDINGS delivers relevant and timely information that equips commercial building owners and facilities management professionals with the knowledge and support they need to solve critical issues; energy management, lowering operating costs, new products for commercial buildings, security, and much more.
BUILDINGS provides facilities management professionals commercial buildings tips and trends trough online webinar events (BuildingsVIP), monthly newsletters, whitepapers and case studies.
In addition to content, BUILDINGS features a comprehensive list of products and services and is your link to the companies that provide these valuable facilities management and commercial buildings resources.
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©Copyright 2014 Stamats Communications, Inc. All rights reserved / BUILDINGS


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10% discount on all orders over $10
Cafe and Ice Creamery providing gourmet ice cream, excellent coffee, great choice of quality food (full breakfast and lunch menu), hot and cold drinks and superb views. Whale watching a specialty!!!
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subset: commoncrawl


text:
March 10, 2014
Hino Trucks announced the appointment of George Daniels to the position of senior vice president sales and customer support. Daniels succeeds Bob McDowell who is no longer with the company.
Daniels, a 40 year veteran of the commercial truck industry has most recently served as Hino Trucks' vice president service operations.
Daniels joined Hino Trucks in 2003 to head up the company's parts and service operations after spending 15 years at Mitsubishi Fuso Truck of America, three years at Iveco Trucks of North America and 13 years at various dealer organizations.
We offer e-newsletters that deliver targeted news and information for the entire fleet industry.
The expert, Mark Betner from Citgo will answer your questions Ask a question
UPS Female Driver First to Reach 4 Million Accident-Free Miles
Ultimate Test Drive Video: SuperTruck's Finer Points
Ultimate Test Drive Video: SuperTruck An Overview
Utility Trailer Details 4000A, 4000S Flatbeds and Tautliner
Forklift Inflator Speeds Up Trailer Load Times
Transflo On-Demand Transmits Documents Efficiently
Carrier Transicold Improves Warranty on Reefer Units
Jost Selling Edbro Hydraulic Cylinders


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Under Pressure: The Dollar Hopes For Retail Sales Boost
The Pound fell against all of its peers yesterday after an index showed that recent UK economic data releases are falling short of economist expectations. The report weakened demand for the currency. Today, Sterling managed to recover some lost ground against the Euro on expectations that inflation data will come in better-than-expected.
US Dollar
The US Dollar remains under pressure from last week's disappointing jobs data. The U.S. economy added far fewer jobs than expected in December cast doubts over the strength of the recovery in the labour market, and fuelled expectations that the Federal Reserve will maintain loose monetary policy for longer. The currency could regain some ground if today's retail sales data comes in positively.
The Euro
The Euro strengthened against the US Dollar and Pound yesterday. The single currency found support on a quiet news day from positive data out of Italy which showed that the regions third largest economy in the Eurozone saw its industrial production increase more than expected. Portugal and Greece both published better-than-forecast inflation data. Today the Euro has softened slightly ahead of the release of Eurozone industrial production data which is expected to show a rise in November.
Australian Dollar
The 'Aussie' retreated from yesterday's one-month high as investors look ahead to tomorrow's Chinese data and as expectations remain high that the US Federal Reserve will continue to taper its monetary easing programme.
New Zealand Dollar
The New Zealand Dollar rose to fresh two-month highs against its U.S. counterpart on Tuesday, after strong business confidence data from New Zealand, while Friday's downbeat U.S. employment data continued to weigh on the greenback. The currency also rose against the Euro as strong business confidence, increased consumer spending and rising property values fuel expectations the Reserve Bank will hike interest rates.
Canadian Dollar
The Canadian Dollar is trading close to its lowest level since October 2009 against its US counterpart and remains at multi-year lows against the Pound and Euro as the currency remains under pressure following last week's poor jobs report.
South African Rand
The South African Rand tumbled to a five-year low against a number of peers as concerns rise that mining output will be affected by labour disputes. As well as worries over labour unrest investors are increasingly being put off of the Rand by a weak economic outlook for the South African economy.
Disclaimer: This update is provided by TorFX, a leading foreign exchange broker, its content is authorised for reuse by affiliates.
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The Sioux City Lewis & Clark Interpretive Center showcases permanent exhibits about the Corps of Discovery's time in the present-day Sioux City area, from late July to early September 1804. The death and burial of Sergeant Charles Floyd on Aug. 20, 1804, is at the center of the story. Floyd was the first U.S. soldier to die west of the Mississippi River.
The expedition as a military operation comes to life in exhibits that use interactive devices, including animatronic mannequins, computers, flip books, stamping stations, text-and-graphic panels, lift-and-drop panels, handpainted murals, a brass-rubbing station, and reproductions of military equipment.
The Traditional Native Games exhibit displays more than two dozen reproductions of games artifacts housed at the Buechel Lakota Memorial Museum at St. Francis Mission on the Rosebud Reservation in South Dakota. The Center's Buffalo Robe exhibit highlights the role of the buffalo to Native peoples.
The Floyd Memorial Association exhibit illuminates the community effort that resulted in the Floyd Monument, the first National Historic Landmark designated by the National Park Service and the U.S. Department of the Interior. The Center's exhibit includes a replica of the obelisk.
The Keelboat Theatre recalls the 55-foot-long vessel of the Lewis & Clark Expedition. DVD presentations on exploration and Native cultures topics are shown daily. The Center's Spirit of Discovery Store offers a range of books and gift items for all ages.
The grounds feature a 30-by-50-foot U.S. Flag atop a 150-foot flag pole. The 14-foot-tall bronze "Spirit of Discovery" sculpture depicts Lewis, Clark and Lewis's Newfoundland dog, Seaman.


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Renamer4Mac - An easy to use batch file renamer | 14 comments | Create New Account
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Renamer4Mac - An easy to use batch file renamer
Despite some lacking features, this has been my favourite renamer for the past few months, Really like the regular expression rename. I have in the past used "a better(?) finder rename" which is extremely slow and confusing, a perl script called rename that I used with unix "find" command. For digital photos, I use jhead which corrects rotation as well as renaming in one pass. My only two complaints with this program are inability recursive rename and save and recall past renames
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Better Than: Your typical Brooklyn DIY show During his solo set last night at Glasslands, Adam Schatz took a moment to lead the audience in a collectively-sung cover of Funkadelic's "I Got a Thing, You Got a Thing, Everybody's Got a Thing," He repeated that line for the audience, as well as the one ... More >>
By Jennifer Swann In high school, Michael Lucid was an artsy, friendly kid who floated around from one campus clique to the next. "I was more approachable and kids felt comfortable talking to me," he says of his time at Santa Monica's Crossroads School, where he graduated in 1996. Because Lucid wa ... More >>
The Thermals hit 285 Kent
Here are the 10 best concerts around the city this weekend, in no particular order.
Don Giovanni records celebrates a decade in the business
Titus Andronicus draw more from hip-hop culture more than you think. Songwriter, bandleader and Wu-Tang Clan fan Patrick Stickles' lyrics are deeply post-modern and full of hypertext links to everything from The Velvet Underground to Albert Camus to Curb Your Enthusiasm. And like any hustler with a ... More >>
For Titus Andronicus's Patrick Stickles, everything is meaning less
In this week's Village Voice, out now: I peek into the twisted pop world crafted by the British genius Mica Levi; Nick Murray talks to the rapper YG about "ratchet music," the new brand of party hip-hop that he's bringing to S.O.B.'s tonight; and Eric Sundermann chats with former Titus Andronicus gu ... More >>
Local hits for the drunk and alone crowd
To supplement this year's Pazz & Jop launch, Sound of the City asked a few critics to expand on the reasonings behind their voting. Here, Michael Tedder breaks down his entire ballot, and along the way he talks about about the operatic heights of Fucked Up, the shredding ability of Annie Clark and R ... More >>
Tell your children not to walk Wye Oak's way. 2011 was a year of looking back relentlessly, whether you were awash in Remember The '90s nostalgia or getting down at a New Kids On The Block show or watching Lady Gaga try to bring back the variety-hour era with her whacked-out Thanksgiving spec ... More >>
In Waste Of Paint, our writer/artist team of Jamie Peck and Debbie Allen will review goings-on about town in words and images. This weekend we learned Manhattan has no monopoly on holiday cheer. Sure, the decorations on Fifth Avenue might cost a little more, but not even the gaudiest depart ... More >>
Michal NanoruThis month marks the publication of Best Music Writing 2011, the annual anthology of top-notch scribing about music2010 pieces by the likes of Nitsuh Abebe, Ann Powers, and Jessica Hopper are collected in the book, which this year was edited by New Yorker classical-music c ... More >>
Permanent Wave's Halloween Covers Show Death by Audio October 27, 2011 Better than: Scrambling to put together my own costume. Last night, Brooklyn's Permanent Wave collective took over Death by Audio with what they were billing as a "ridiculously fun night of cover sets by some of our favorite l ... More >>
Ben Lozovsky"I just got back from my last tour with the band Titus Andronicus," writes Amy Klein in her gratitude-filled blog post announcing her departure from the band. The post goes on to say that no, there was no big fight or drama-filled rock and roll story that fueled her split; she's j ... More >>
Ben LozovskyTitus Andronicus Glasslands Gallery Wednesday, October 18 Better than: Reading a good book and being in bed by 10. As you're surely by now aware, this year's CMJ Music Marathon has some thousand-plus bands, not from all over the country but all over the worldeveryone from ... More >>
Permanent Wave celebrates Halloween with a night of covers
The last time we checked in with Amy Klein, the Titus Andronicus guitarist/violinist told us about the genesis of the Brooklyn-based activist group Permanent Wave, which has since put on protests, panel discussions, and concerts. Between organizing benefit concerts and playing with both Titus ... More >>
Vivian Girls up the "fi"
In honor of Beyoncé's four-night run at Roseland, which continues with a sold-out show tonight, Sound of the City is celebrating the singer with a series of features. While she's a singular artist with her own way of handling tracks, it's fun to imagine what would happen if other artists tac ... More >>
Willie Davis4Knots Music Festival: Titus Andronicus Pier 17, South Street Seaport Saturday, July 16 Better than: Shakespeare. After a race through the New York City subway system, I charged triumphantly out onto the waterfront as Patrick Stickles of Titus Andronicus sang the slow opening ly ... More >>
In Waste Of Paint, our writer/artist team of Jamie Peck and Debbie Allen will review goings-on about town in words and images. This weekend, Debbie and I turned our attentions inwards, to the Village Voice's own 4Knots Music Festival at South Street Seaport. As always, the Seaport was a str ... More >>
Willie DavisTitus Andronicus' Patrick Stickles (left) and Amy Klein.You came. You danced. You sweated. And based on the tweets we saw coming out of our very first 4Knots Music Festival yesterday at the South Street Seaport, everyone had as much fun as we expected! Our favorite 140-character-o ... More >>
A few of us Voice women headed down to the Manhattan Criminal Courthouse yesterday to join hundreds of New Yorkers protesting the acquittal of Kenneth Moreno and Franklin Mata, the two NYPD cops accused of raping a woman in her apartment in 2009. There was chanting, sign-waving, speechifying; ... More >>
OK, well, soon-to-be music editor anyway--our pal Maura Johnston, who starts here in just one more short week, will be at the Housing Works Bookstore tonight, reading words with SOTC buddies Amy Klein (a/k/a the formidable punk presence that is Titus Andronicus's Amy Andronicus), It's the Rea ... More >>
"I think empowerment is very sexy and cool, and there's no reason you can't believe that." Amy Klein is a busy woman. Her most high-profile gig is playing guitar for Thomas-Paine-for-the-Twitter-Generation art-punks Titus Andronicus, but she makes a diverse plethora of music on her own. Her ... More >>
During a recent Mercury Lounge invasion by majestic New Jersey angst-punk deities Titus Andronicus, we grew to greatly appreciate the presence of guitarist/violinist/backup vocalist Amy Klein, a bouncing, gleeful antidote to all that hyper-masculine self-recrimination. That someone in this ba ... More >>
Murray Hill introduces the night's star attraction. The Kathleen Hannah Project The Knitting Factory Saturday, December 12 Better than: Any actual battle of the bands that I've ever attended. We are gathered here tonight at the Knitting Factory to praise Kathleen Hanna, not bury her. Though it ... More >>


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Frank Timis, Chairman of the Timis Corporation, cut his teeth in the mining industry in his teens in Western Australia, where he worked as a prospector looking for diamonds, minerals and gold. By the age of 27, Frank started his first mining venture. This kick-started a career spanning three decades building up a multi-billion dollar portfolio of rich natural resource assets around the world.
The Timis Corporation is a portfolio of businesses in the mining, oil and gas, life sciences and agricultural industries and include African Minerals, African Petroleum, International Petroleum and London Pharma. With a strong ethical code for social responsibility, the Timis group of companies works closely with local Governments to give back to the communities in which they operate.
Frank was born with the sense that life is not measured by how much one achieves, but by how much one helps others in need. This guiding principle has remained a consistent throughout his life and the rate in which he supports and gives to charities has grown exponentially with the size and success of his business ventures.
NewstimeAfrica.com reports Frank Timis, the Chairman of African Minerals and the emperor of West African Mining has recently visited Sierra Leone after his tour of four (4) other countries in West Africa where he has his business interests. He went to Sierra Leone to spend a few days with his employees. As a billionaire, …More


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Registration for Junior Kindergarten for the Maple Dale – Indian Hill School District will be held Wednesday, January 23 from 7:30 am to 3:30 pm at Indian Hill School, 1101 West Brown Deer Road.
To be eligible for kindergarten for the 2013-2014 school year, a child must be 4 on or prior to September 1. Parents are required to bring the child's birth certificate and proof of residency (if you own your home, a copy of the deed [last page] or '12 tax bill and a copy of utility bill; if renting, a copy of the lease agreement [last page] and copy of utility bill). Children will not need to accompany parents.
Parents will be asked to complete a registration form, emergency information, and immunization dates. Call Indian Hill at 351-7390 with any questions regarding kindergarten registration. If you cannot attend the registration at the school, but live in the district, please contact the office to make other arrangements.
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- Noted Jewish Argentine Writer To Read at UWM Oct. 23
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- Stritch Theater presents Steel Magnolias


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Posts tagged drawing
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Adobe Mighty & Napoleon Projects, a pressure sensitive digital drawing tool that uses Bluetooth LE to stay connected to your devices and a digital ruler that can create a digitally-projected edge used to draw shapes and lines.
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Mate Check Private Investigations
Nationwide Service
+1 (480) 391.1010 or +1 (866) 640.1010
email: firstname.lastname@example.com
Specializing in Domestic Relations Investigative Services
Mate check welcomes same sex and alternative lifestyle cases.
Infidelity, adultery, cheating, being unfaithful, having and affair.......whatever you want to call it can be one of the most painful things to go through. People don't understand the pain someone goes through when they love someone and and that someone cheats on them. The not knowing if your significant other is cheating, or unfaithful causing infidelity or not is equally devastating. Sandra Hope, the expert female Private Investigator, Detective, PI, Sleuth, Gumshoe and Decoy, can get you the truth you need for peace of mind or for confirming your suspicions. We here at Mate Check understand the way you feel and know how to deal with your situation best. Once you have the truth you can have much more success with marriage counseling or even discussions about your relationship with your partner.
Mate Check Private Investigations is a Nationwide full service
private investigations company, agency, firm, office, location, founded in 1994 and it is female
owned and operated offering professional private investigative
services. Sandra Hope who is the owner and founder has been an
expert female Private Investigator, Detective, PI, Sleuth, Gumshoe
and Decoy
for over 14 years. Mate Check
Private Investigations specializes in domestic relations matters
that include infidelity, cheating matters, divorce, child custody,
high profile investigator, high profile investigations,
and other matters of the heart such as finding lost loved ones by
finding a person, or undercover operations tailor-made to suit your
situation. We offer the following services. National criminal
background checks, search, video surveillance, decoy placement, male
decoy, female decoy, sexy decoy,
Internet decoy, GPS tracking, locate a vehicle, teen check, nanny
check, date check, DNA testing, Vehicle registration, Utility
search, Asset search, Computer forensics, internet use, computer
usage check, Lie detection test, polygraph examination, questioned
documents, Missing persons, Counter intelligence, debugging, Online
dating prescreening, Mystery and secret shopper, Anti stalking and
harassment, personal protection, security, Process serving, Drug
testing, Insurance fraud, Sexual harassment, Wrongful death,
Malpractice, Family Law Investigations, infidelity investigations,
fraud investigations, sexual harassment, mate checks, date checks,
corporate investigations, high profile cases, high profile prominent
cases. What is the hourly rate for high end investigations? 95.00. Our rate is
the same for every type of case or how complex it may be. We have the expertise
and the state of the art equipment to get results fast.
In today's social climate it is not only natural, but also prudent, to have concerns about potential partner's claims and representations. Sad, but true, this can also apply to our spouses and life partners,* if they have given us reason to doubt their word, due to suspicious behavior -or- if their integrity is in question. Mate Check also helps people with divorce and custody situations when a relationship can not be saved. In divorce proceedings it is crucial to get all of your facts ready for the court. You need to locate all assets so they can be properly divided at time of trial or you can forever lose claim to them. If custody is an issue and there is reason for you to believe your children are not safe when they are not with you, Mate Check can get the evidence for you. It can be critical for you to get the proper custody division in the best interest of your children. When it is important use an expert who specializes in the area of investigations that you need.
Mate Check is also fully staffed with professional Spanish speaking private investigators. Whether you need to speek with a Spanish speaking private investigator or your significant other is planning a trip to Mexico without you. Mate Check has worked in many areas in Mexico such as Acapulco, Cancun, Cabo San Lucas, Puerto Vallarta, Kino, Rosarito Beach, Rocky Point, La Paz, Mexico City, and many more. You can rest assure if your spouse or significant other is in Mexico and you want to be a fly on the wall, Mate Check will be there.
* Video Surveillance, cheating,
infidelity, unfaithful, spouse, boyfriend, girlfriend, wife, husband
In 1994, when President and founder Sandra Hope launched Mate Check
Private Investigations, the mainstream acceptance and adoption of an
investigations team that focused mainly on domestic relations was rather
novel. Journalists and newscasters jumped on the story of a woman who
had started her own private investigation agency after assisting friends
and relatives in finding the answers they were looking for. Sandra
Hope is a female investigator so she has an understanding of what people
are going through and she is very easy to talk with.
Mate Check has been covered by leading news sources including:
As an Industry Pioneer in Infidelity and domestic relations cases, Mate Check is a
fully licensed and bonded investigation company. For the past 10 years,
Mate Check has received an enormous amount of media coverage, but more
importantly, it has compiled an impressive roster of satisfied clients
by answering the question "Is
or she all they claim to
be? "
Signs of Spousal infidelity
Statistics say that 85% to 90% of women or men who feel their lover is cheating are correct. 50% of men who feel their lover is cheating are right. If you have suspicious, consider some of the following as signs that something might be going on.
Have you noticed any of the following:
You may also want to consider reviewing your spouse's credit card bills.
Want more info go to: Signs of Cheating
What is a Private Investigator?
A Private Investigator is a professional trained in the art of investigations and video surveillance. In most states, a license is mandatory. Like with an attorney or doctor, the State has mandated that certain qualifications, training and experience are required for licensure to protect the public from those who do not have the experience or qualifications to do the job correctly. A private investigator's training is usually varied and tends to focus on a certain area of practice, again much like a attorney. At Mate Check, our investigators specialize in investigating and documenting marital infidelity, divorce and child custody matters. Often times a private investigator's experience comes from work in law enforcement, the military, forensic or a research background. The core of a private investigators capability is to take whatever information you, the client, have and to go out and find whatever information or evidence you need. The work that a private investigator does is strictly confidential and stays between you and the investigator, which is usually mandated by law.
Read more about the history of infidelity.
What does a Private Investigator specializing in infidelity and cheating actually do?
The job of a private investigator specializing in infidelity, divorce and child custody is to gather information about the subject's activities and interactions. We frequently work on these types of cases for attorneys. Most private investigators are trained to perform functions like video surveillance, research and interviewing. At Mate Check we have specialists who focus on spousal surveillance or information gathering. Our surveillance experts spend the majority of their time trailing and watching suspected cheaters or potentially unfit parents. Often, we will then be asked to identify the "other man/woman" for our client. We have access to private investigator based computer databases and searches, that the public does not have access to, which allow them to quickly obtain massive amounts of information. Because of the nature of private investigative work, we often end up testifying in court about our cases. A good private investigator can confidentially get you the answers you need, quickly, accurately and affordably.
Definition of a Private Investigator
A private investigator, private detective, PI, or private eye, is a person who can be hired by citizens or groups to undertake investigations.
Private investigators, private detectives, p.i's, private eye, gumshoe, sleuths often work for attorney's in civil litigation cases for the plaintiff or the defense, gathering much needed evidence that the attorney's use to prove or defend their case in court. Many work for insurance companies to investigate suspicious auto accident and other injury claims. If a person claims they sustained injuries in a low impact car accident the claim becomes suspicious. Before states adopted the of no-fault divorce, many private investigators were hired to find out evidence of infidelity, adultery, cheating and other unfaithful matters or illegal conduct within marriage to establish a basis for a divorce. Despite the lack of legal necessity for such evidence in many jurisdictions, according to news reports collecting evidence of adultery or other "bad behavior" by spouses and partners is still one of the most sought after work investigators undertake, as the stakes being fought over now are child custody, alimony, or marital property division disputes. Now that on-line dating has become so popular it has become equally popular for people to have a private investigator conduct a criminal background search before coming into physical contact with that person they have met on line chatting, instant messaging, e-mailing, or someone they have met on match.com, great expectations, e-harmony or any of the online dating forums.
Many jurisdictions require PIs to be licensed, and they may or may not carry guns depending on local laws. Some are ex-police officers and detectives, although some are not. They are expected to keep detailed reports and to be prepared to testify in court cases regarding any of their investigations on behalf of their clients. Private investigators have to be careful to remain within the boundaries of the law and within the scope of their investigation. Some private investigators have faced with criminal charges for crossing the line. Irregular long hours may also be required when performing video surveillance work.
Private investigators also undertake a large variety of work from their clients that you would not expect. For example, many private investigators are involved in process serving, the personal service of summons of complaints, subpoenas and other legal documents to parties in a legal case. The tracking of absconding debtors can also form a large part of a private investigators case load. Many firms specialize in a particular field of expertise. For example, some private investigative firms / agencies deal only in tracking down individuals. Others may specialize in highly technical surveillance countermeasures, or TSCM counter surveillance, which is the finding and dealing with unwanted forms of electronic surveillance (for example, a bugged bedroom or office for industrial espionage purposes). Other private investigators, also known as Corporate Investigators, specialize in corporate matters, including sexual harassment, anti-fraud work, the protection of intellectual property and protecting trade secrets, anti-piracy, copyright infringement investigations, due diligence investigations and computer forensics work. Some spouses suspect that evidence of cheating communications such as e-mails, chat rooms, instant messages and porn web sites might be on the spouses computer that have been erased. A computer forensic private investigator can restore erased files on a computer to determine the true history of what a person has done on their computer and they recover the information and give it to their client. Sometimes the suspicions are more serious and a spouse suspects that child porn may be on their spouses computer. A forensic investigator knows how to recover this sensitive information and deal with it in accordance with the law to protect the chain of custody and turn over the evidence to the authorities.
Increasingly, modern PIs prefer to be known as "professional investigators" rather than "private investigators" or "private detectives". This has been an effort to globalize the the area of practice as one of a professional nature.
Worldwide Scope
In some countries throughout the world, private investigations are illegal. In other countries, private investigations are thriving, including: United States, the Netherlands, Mexico, Canada, Turkey, United Kingdom, France, Spain, South Africa, Australia, and Japan. In South Africa, private investigators are in very high demand due to not enough police to work and keep up with the high crime rates. Other countries throughout the world have private investigators, but many of their duties are restricted to a narrow scope. In South Korea, for example, video surveillance is allowed only in insurance fraud situations , which include all types of claims such as medical malpractice, professional liability, general liability, basically in any case where an insurance company must defend a defendant from any kind of claim that can be made against the policy holder they may even be obligated to investigate and litigate frivolous law suits as well. Insurance companies employ the services of private investigators in attempt to verify or defeat these claims. The private investigators evidence is usually the only evidence an insurance company can rely on to honor or refuse to pay a claim. Some countries in the world require licensing of private detectives, but most do not.
Working Environment
Private detectives and investigators often work strange hours because of the need to conduct video surveillance and interview people who are not available during normal working hours. Undercover decoy investigations also take investigators into the late night. They may have to make friends with a subject at a bar he patrons on Saturday Nights. The investigator must keep the same hours as his subject. Early morning, evening, weekend and holiday work is usual.[
Many detectives and investigators spend time away from their offices conducting interviews, decoys, undercover operations and conducting video surveillance, but some work in their office most of the day conducting computer forensics, computer searches and making investigative telephone calls. The private investigators who have their own firms / agencies and employ other private investigators might work soley in an office and have normal business hours.
When a private investigator is working on a case away from the office, the environment might range from plush offices to seedy bars. Department Store and Chain hotel detectives work in the businesses that they protect. Investigators generally work alone, but they sometimes work with other detectives during video surveillance or when following a subject in order to avoid getting caught they would also use two vehicles, but these days if your client has legal authority to put a gps tracking devise on a vehicle it makes surveillance a much smoother operation taking away the main element of your subject detecting your presence, since you will not need to follow him at a close distance. The gps tracker will always tell you were your subject is so you can pop in and catch him/her by surprise.
Some of the work involves up close confrontations, so the job can be mentally stressful and equally dangerous. Some situations call for the investigator to carry a gun, such as certain bodyguard assignments for prominent client's corporate executives or celebrity clients. Detectives and investigators who carry weapons and guns must be licensed by the appropriate authority. In most cases, however, a weapon is not necessary, because the purpose of the work is gathering information and not law enforcement or criminal apprehension, so the investigator will not encounter a possible harmful situation.
Education Training, and qualifications,
There are no formal education requirements for most private detective or investigator jobs, although many private investigators have college degrees or have taken legal or criminal investigation courses. Private detectives and investigators typically have previous experience in other professions. Some work initially for insurance or collections companies, in the private security industry, or as investigative paralegals. Many investigators enter the field after serving in the law enforcement community and the military branches of government auditing and investigative positions, or federal intelligence jobs CIA.
Former law enforcement officers, military investigators, and government agents, who retire, often become private investigators or detectives in a second career. Others enter wide range of fields as finance, forensic accounting, consumer credit, investigative reporting, insurance fraud, and law. These individuals often can apply their prior work experience in a related investigative specialty. A few private investigators enter the profession directly after graduating from college, generally with associate's or bachelor's degree in criminal justice, police science or with a private investigation diploma.
majority of states in the United States and the District
of Columbia require private detectives and private
investigators to be licensed by the state that they wish
to conduct business in. Some states allow their licensed
private invest Licensing requirements vary, however.
Seven states Alabama, Alaska, Colorado, Idaho,
Mississippi, Missouri, and South Dakota have no
statewide licensing requirements, some states have very
few requirements, and many other states have stringent
regulations. A growing number of states are enacting
mandatory training programs for private detectives and
investigators. For example, the Bureau of Security and
Investigative Services of the California Department of
Consumer Affairs requires private investigators to be at
For private detective and investigative jobs, most employers look for individuals with tenacity, persistence, attention to detail and assertiveness. A candidate must not be unaffected by conflict and confrontation, should possess good communicative skills, and should be able to think on his/her feet. Good interviewing and interrogation skills also are important and usually are learned in earlier careers in law enforcement or other fields. A true chameleon makes a perfect private investigator because they can be anyone at any time. Since the courts are often the ultimate judge of a properly conducted investigation, the investigator must be able to present the facts in a manner that a jury will understand.
Training in subjects such as criminal justice and police science can be helpful for people learning to be private detectives and investigators. Most corporate investigators must have a bachelor's degree, preferably in a business-related field. Some corporate investigators have a master's degree in business administration or a law degree, while others are CPAs. Corporate investigators hired by large companies may receive formal training from their employers on business practices, management structure, and various finance-related topics. The screening process for potential employees typically includes a background check for a criminal history.
Some private investigators receive certification from a professional organization to demonstrate competency in a field. For example, the National Association of Legal Investigators (NALI) confers the Certified Legal Investigator designation to licensed investigators who devote a majority of their practice to negligence or criminal defense investigations. To receive the designation, applicants must satisfy experience, educational, and continuing-training requirements and must pass written and oral exams administered by the NALI.
Most private-detective agencies are small, with little room for advancement. Usually, there are no defined ranks or steps, so advancement takes the form of increases in salary and assignment status. Many private detectives and private investigators work for private investigative agencies at the beginning of their careers and, after a few years, start their own firms. Corporate and legal investigators may rise to supervisor or manager of the security or investigations department.
median salary for a private investigator in the U.S. is
History of the private investigator
After Vidocq, the industry was born. Much of what private investigators did in the early days was to act as the police in matters that their clients felt the police were not equipped for or willing to do. A larger role for this new private investigative industry to was to assist companies in labor disputes. Some early private investigators provided armed guards to act as a private military.
In the
U.S., the Pinkerton National Detective Agency was a
private detective agency established in
the labor disputes of the late
Pinkerton agents were also hired to track western outlaws like Jesse James, the Reno brothers, and the Wild Bunch, including Butch Cassidy and the Sundance Kid. The Pinkerton agency's logo, an eye embellished with the words "We Never Sleep," inspired the term "private eye."
It was
not until the prosperity of the
Since then the private detective industry has grown with the changing needs of the public. Social issues like infidelity and divorce matters have impacted the industry and created new types of work, as has the need for insurance and, with it, insurance fraud, criminal defense investigations and the invention of low-cost listening devices. In a number of countries, a licensing process has been introduced that has put criteria in place that investigators have to meet: in most cases, a clean criminal record. This has combined with modern business practices that have ensured that most investigators are now professional in outlook, rather than seeing the private investigative world as a second career opportunity for retired ex-law enforcement.
For more information on spousal infidelity and infidelity investigations, your find it useful to review our Overview of Surveillance
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My name is Marty Van Hoof and I am running for the 1st District Alderman. I am asking the citizens of Cudahy's 1st District to vote for me in the Primary on February 19th and in the General Election on April 2nd.
My wife and I purchased a house in Cudahy 7 years ago. We have a son who attends Lincoln Elementary.
I have been volunteering time to the City of Cudahy for many years. It started with being appointed to the Comprehensive Plan Steering Committee in 2007. Then in 2008 I was appointed by then Mayor Ryan McCue to the Community Development Authority (CDA). I continue to volunteer my time on the CDA and currently serve as the Vice-Chairperson. I was also appointed to the Design Review Board (DRB) in 2012 by Mayor Tony Day.
I consider myself a fiscal conservative and a right-leaning moderate. I am pro business and believe in the free market. During my time on the CDA I have seen how hard the City (including the CDA, Economic Development Director, and elected officials) has worked to bring development to the City. It's not an easy task and it doesn't happen overnight. Many things have worked out, but unfortunately many others have not. Unfortunately for Cudahy Wal-Mart decided to build in South Milwaukee, but we have to put that behind us and start working to leverage this development within our City. There is great opportunity for development along the southern end of Packard Ave and at the intersection with College Ave.
I see the potential in Cudahy, that's why my wife and I bought a house here 7 years ago. Cudahy already has so much to offer with its proximity to Lake Michigan, wonderful County Parks, the airport, and downtown Milwaukee. Cudahy also has a first-rate hospital, outstanding schools and great neighborhoods for raising a family. We need to promote these great qualities and show home buyers and businesses the great value that Cudahy has to offer.
Let's bring the Pride back to Cudahy.
As I believe that communication is key in business and in government, I am looking forward to talking with many of you in the coming weeks.
Feel free to contact me if you want to find out more about me or my ideas for Cudahy.
Martin Van Hoof
3837 E. Allerton Avenue
And I would be honored to receive your vote at the Primary on February 19th and the General Election on April 2nd.
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- May 11, 1953 - January 25, 2010
- Deer Park, New York
of Charles' Passing
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"There isn't a day that goes by that I don't think of u. You will forever be in my heart. There will never be another. U are and always will be a...Read More »
1 of 3 | Posted by: Roe - Deer Park , NY - Wife
"I miss and love you big brother :( everyday <3
2 of 3 | Posted by: Barbara - huntington, NY
"God bless Charlie and his family. Rosary intention for his soul and for those who are in need of prayers in your family. Amen
3 of 3 | Posted by: Rose Marie Muhl - Wadsworth, OH
Charles was born on May 11, 1953 and passed away on Monday, January 25, 2010.
Charles was a resident of Deer Park, New York.
The information in this obituary is based on data from the US Government's Social Security Death Index. No further information is available. More details on this data source are provided in our Frequently Asked Questions section.


text: Pregnancy > Second Trimester Your Pregnancy: Week 18 As your growing uterus starts shifting your center of gravity (belly forward, bottom out), hormones are causing your ligaments to relax and joints to loosen. The result? Back pain and soreness. On the bright side, if you want to know baby's gender, this might be your first week for a sneak peek. < Previous Week Next Week > > Help for hip pain?> Are acupuncture and massages safe?> Getting enough folic acid?> See all second trimester Q&AsBaby's now the size of a sweet potato!Baby's become amazingly mobile (compared to you, at least), passing the hours yawning, hiccupping, rolling, twisting, kicking, punching, sucking, and swallowing. And baby is finally big enough that you'll soon be able to feel her movements.To-do:> Consider a doula and start interviewing> Pick up some good baby books> Go to your checklist[ tip ] Now that baby can hear what's going on outside the womb, it's time to get out the tunes. Her faves? Classical, lullabies, new age...and anything else that resembles your own thumping heart (about 60 beats per minute).> Chat with other moms-to-be who share your due date> Read more about being 18 weeks pregnantAll medical information reviewed by Dr. Geeta K. Swamy, Duke University Medical Center OB/GYN Department Previous Article: Your Pregnancy: Week 17 Next Article: Your Pregnancy: Week 19 10 Babymoon Tips We'll help make sure your prebaby vacay goes off without a hitch. Pregnancy Workout Plan Get fit and stay that way, even as your bump continues to grow. Pregnancy Myths Debunked From cutting back on caffeine to putting the kabosh on workouts, find out what's fact and what's fiction. popular questions Q&A: Morning sickness tips? Q&A: Do I need a birth plan? Q&A: Registering for baby? recently added questions What Happens at Baby's One-Month Checkup? When Can I Switch Baby From the Infant Car Seat to a Convertible? What Should Baby Eat for Dinner?


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Are you W Löscher?Claim your profile
Publications (552)2005.14 Total impact
Article: Sucrose consumption test reveals pharmacoresistant depression-associated behavior in two mouse models of temporal lobe epilepsy.[Show abstract] [Hide abstract]
ABSTRACT: Among the co-morbidities observed in epilepsy patients depression is the most frequent one. Likewise, depression by itself is accompanied by an increased risk to develop epilepsy. Both epilepsy and depression are characterized by a high incidence of pharmacoresistance, which might be based on overactivity of multidrug transporters like P-glycoprotein at the blood-brain barrier. Using genetically modified mice in preclinical epilepsy research is pivotal for investigating this bidirectional relationship. In the present study, we used the sucrose consumption test (SCT) in the pilocarpine and the intrahippocampal kainate mouse post-status epilepticus model to reveal anhedonic behavior, i.e. hyposensitivity to pleasure, as a key symptom of depression. Mice were repetitively investigated by SCT during early epilepsy and the chronic phase of the disease, during which response to antidepressant drug treatment was assessed. SCT revealed long-lasting anhedonia in both models. Anhedonia appeared to be pharmacoresistant, as neither chronic treatment with imipramine in the pilocarpine model nor chronic treatment with fluoxetine in the kainate model could annihilate the differences in sucrose consumption between control and epileptic mice. Moreover, knock-out of P-glycoprotein did not improve the treatment effect of fluoxetine. In conclusion, our findings show for the first time that the SCT is suited for detection of depression-like behavior in mouse models of temporal-lobe epilepsy. Both models might serve as tools to further investigate the neurobiology and pharmacology of epilepsy-associated pharmacoresistant depression.Experimental neurology. 09/2014;
Article: Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs.[Show abstract] [Hide abstract]
ABSTRACT: The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs.Journal of Veterinary Pharmacology and Therapeutics 07/2014; · 1.35 Impact Factor
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ABSTRACT: Objective. There is considerable interest in using bumetanide, a chloride importer NKCC antagonist, for treatment of neurological diseases, such as epilepsy or ischemic and traumatic brain injury, which may involve deranged cellular chloride homeostasis. However, bumetanide is heavily bound to plasma proteins (~98%) and highly ionized at physiological pH, so that it only poorly penetrates into the brain, and chronic treatment with bumetanide is compromised by its potent diuretic effect. Methods: To overcome these problems, we designed lipophilic and uncharged prodrugs of bumetanide that should penetrate the blood-brain barrier more easily than the parent drug and are converted into bumetanide in the brain. The feasibility of this strategy was evaluated in mice and rats. Results: Analysis of bumetanide levels in plasma and brain showed that administration of two ester prodrugs of bumetanide, the pivaloyloxymethyl (BUM1) and N,N-dimethylaminoethylester (BUM5), resulted in significantly higher brain levels of bumetanide than administration of the parent drug. BUM5, but not BUM1, was less diuretic than bumetanide, so that BUM5 was further evaluated in chronic models of epilepsy in mice and rats. In the pilocarpine model in mice, BUM5, but not bumetanide, counteracted the alteration in seizure threshold during the latent period. In the kindling model in rats, BUM5 was more efficacious than bumetanide in potentiating the anticonvulsant effect of phenobarbital. Interpretation: Our data demonstrate that the goal to design bumetanide prodrugs that specifically target the brain is feasible and that such drugs may resolve the problems associated with using bumetanide for treatment of neurological disorders. ANN NEUROL 2014. © 2014 American Neurological Association.Annals of Neurology 02/2014; · 11.19 Impact Factor
Article: Marked Differences in the Effect of Antiepileptic and Cytostatic Drugs on the Functionality of P-Glycoprotein in Human and Rat Brain Capillary Endothelial Cell Lines.[Show abstract] [Hide abstract]
ABSTRACT: The expression of P-glycoprotein (Pgp) is increased in brain capillary endothelial cells (BCECs) of patients with pharmacoresistant epilepsy. This may restrict the penetration of antiepileptic drugs (AEDs) into the brain. However, the mechanisms underlying increased Pgp expression in epilepsy patients are not known. One possibility is that AEDs induce the expression and functionality of Pgp in BCECs. Several older AEDs that induce human cytochrome P450 enzymes also induce Pgp in hepatocytes and enterocytes, but whether this extends to Pgp at the human BBB and to newer AEDs is not known. This prompted us to study the effects of various old and new AEDs on Pgp functionality in the human BCEC line, hCMEC/D3, using the rhodamine 123 (Rho123) efflux assay. For comparison, experiments were performed in two rat BCEC lines, RBE4 and GPNT, and primary cultures of rat and pig BCECs. Furthermore, known Pgp inducers, such as dexamethasone and several cytostatic drugs, were included in our experiments. Under control conditions, GPNT cells exhibited the highest and RBE4 the lowest Pgp expression and Rho123 efflux, while intermediate values were determined in hCMEC/D3. Known Pgp inducers increased Rho123 efflux in all cell lines, but marked inter-cell line differences in effect size were observed. Of the various AEDs examined, only carbamazepine (100 μM) moderately increased Pgp functionality in hCMEC/D3, while valproate (300 μM) inhibited Pgp. These data do not indicate that treatment with AEDs causes a clinically relevant induction in Pgp functionality in BCECs that form the BBB.Pharmaceutical Research 01/2014; · 4.74 Impact Factor
Article: Searching for the Ideal Antiepileptogenic Agent in Experimental Models: Single Treatment Versus Combinatorial Treatment Strategies.[Show abstract] [Hide abstract]
ABSTRACT: A major unmet medical need is the lack of treatments to prevent (or modify) epilepsy in patients at risk, for example, after epileptogenic brain insults such as traumatic brain injury, stroke, or prolonged acute symptomatic seizures like complex febrile seizures or status epilepticus. Typically, following such brain insults there is a seizure-free interval ("latent period"), lasting months to years before the onset of spontaneous recurrent epileptic seizures. The latent period after a brain insult offers a window of opportunity in which an appropriate treatment may prevent or modify the epileptogenic process induced by a brain insult. A similar latent period occurs in patients with epileptogenic gene mutations. Studies using animal models of epilepsy have led to a greater understanding of the factors underlying epileptogenesis and have provided significant insight into potential targets by which the development of epilepsy may be prevented or modified. This review focuses largely on some of the most common animal models of epileptogenesis and their potential utility for evaluating proposed antiepileptogenic therapies and identifying useful biomarkers. The authors also describe some of the limitations of using animal models in the search for therapies that move beyond the symptomatic treatment of epilepsy. Promising results of previous studies designed to evaluate antiepileptogenesis and the role of monotherapy versus polytherapy approaches are also discussed. Recent data from both models of genetic and acquired epilepsies strongly indicate that it is possible to prevent or modify epileptogenesis, and, hopefully, such promising results can ultimately be translated into the clinic.Journal of the American Society for Experimental NeuroTherapeutics 01/2014; · 5.38 Impact Factor
Article: Prolonged depth electrode implantation in the limbic system increases the severity of status epilepticus in rats[Show abstract] [Hide abstract]
ABSTRACT: Chronically implanted intracranial depth electrodes are widely used for studying electroencephalographic activities in deep cerebral locations and for electrical stimulation of such locations. We have previously reported that prolonged implantation of an electrode in the basolateral amygdala (BLA) of rats facilitates subsequent kindling from this site, indicating a pro-kindling or pro-epileptogenic effect. To further characterize this phenomenon, we analyzed data from experiments in which we induced a self-sustaining status epilepticus (SSSE) by BLA stimulation following different periods of post-surgical delay. In a total of 183 Sprague-Dawley rats, three groups with different periods of postsurgical delay to onset of electrical stimulation were compared: group 1 (16 days on average), group 2 (28 days) and group 3 (48 days). Three types of SSSE were observed after BLA stimulation: type 1 (nonconvulsive), type 2 (nonconvulsive occasionally interrupted by generalized convulsive activity), and type 3 (generalized convulsive). While groups 1 and 2 did not differ in the frequency of these SSSE types, the group with the longest interval between electrode implantation and stimulation (group 3) showed significantly more severe SSSE than the two other groups. The data indicate that intracranial electrode implantation may increase the sensitivity of the implanted area to seizure induction, extending previous findings in the kindling model. Potential mechanisms of these findings include the functional consequences of local microhemorrhages and blood-brain barrier destruction.Epilepsy research 01/2014; · 2.48 Impact Factor
Article: Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.[Show abstract] [Hide abstract]
ABSTRACT: P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid rafts to gain its full functionality.PLoS ONE 01/2014; 9(2):e88154. · 3.53 Impact Factor
Article: A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value[Show abstract] [Hide abstract]
ABSTRACT: Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT.Journal of Psychiatric Research 01/2014; · 4.09 Impact Factor
Article: Antiepileptic efficacy of lamotrigine in phenobarbital-resistant and–responsive epileptic rats: A pilot study[Show abstract] [Hide abstract]
ABSTRACT: About 25% of patients with epilepsy are refractory to treatment, so that new, more effective antiepileptic drugs (AEDs) are urgently needed. Animal models that simulate the clinical situation with individuals responding and not responding to treatment are important to determine mechanisms of AED resistance and develop novel more effective treatments. We have previously developed and characterized such a model in which spontaneous recurrent seizures (SRS) develop after a status epilepticus induced by sustained electrical stimulation of the basolateral amygdala. In this model, prolonged treatment of epileptic rats with phenobarbital (PB) results in two subgroups, PB responders and PB nonresponders. When PB nonresponders were treated in previous experiments with phenytoin (PHT), 83% of the PB-resistant rats were also resistant to PHT. In the present study we examined if rats with PB resistant seizures are also resistant to lamotrigine (LTG), using continuous EEG/video recording of spontaneous seizures over 10 consecutive weeks. For this purpose, a new group of epileptic rats was produced and selected by treatment with PB into responders and nonresponders. As in previous studies, PB nonresponders had a significantly higher seizure frequency before onset of treatment. During subsequent treatment with LTG, all PB nonresponders and 60% of the PB responders exhibited >75% reduction of seizure frequency and were therefore considered LTG responders. Plasma levels of LTG did not differ significantly between responders and nonresponders. The data of this pilot study indicate that LTG is more effective than PHT to suppress seizures in PB nonresponders in this model, but that not all PB responders also respond to LTG. Overall, our data provide further evidence that AED studies in post-SE TLE models are useful in determining and comparing AED efficacy and investigating predictors and mechanisms of pharmacoresistance.Epilepsy Research. 01/2014;
Article: The Pharmacology of Imepitoin: The First Partial Benzodiazepine Receptor Agonist Developed for the Treatment of Epilepsy.[Show abstract] [Hide abstract]
ABSTRACT: Although benzodiazepines (BZDs) offer a wide spectrum of antiepileptic activity against diverse types of epileptic seizures, their use in the treatment of epilepsy is limited because of adverse effects, loss of efficacy (tolerance), and development of physical and psychological dependence. BZDs act as positive allosteric modulators of the inhibitory neurotransmitter GABA by binding to the BZD recognition site ("BZD receptor") of the GABAA receptor. Traditional BZDs such as diazepam or clonazepam act as full agonists at this site, so that one strategy to resolve the disadvantages of these compounds would be the development of partial agonists with lower intrinsic efficacy at the BZD site of the GABAA receptor. Several BZD site partial or subtype selective compounds, including bretazenil, abecarnil, or alpidem, have been developed as anxioselective anxiolytic drugs, but epilepsy was not a target indication for such compounds. More recently, the imidazolone derivatives imepitoin (ELB138) and ELB139 were shown to act as low-affinity partial agonists at the BZD site of the GABAA receptor, and imepitoin was developed for the treatment of epilepsy. Imepitoin displayed a broad spectrum of anticonvulsant activity in diverse seizure and epilepsy models at tolerable doses, and, as expected from its mechanism of action, lacked tolerance and abuse liability in rodent and primate models. The more favorable pharmacokinetic profile of imepitoin in dogs versus humans led to the decision to develop imepitoin for the treatment of canine epilepsy. Based on randomized controlled trials that demonstrated antiepileptic efficacy and high tolerability and safety in epileptic dogs, the drug was recently approved for this indication in Europe. Hopefully, the favorable profile of imepitoin for the treatment of epilepsy in dogs will reactivate the interest in partial BZD site agonists as new treatments for human epilepsy.CNS Drugs 12/2013; · 4.38 Impact Factor
Article: Consequences of inhibition of bumetanide metabolism in rodents on brain penetration and effects of bumetanide in chronic models of epilepsy.[Show abstract] [Hide abstract]
ABSTRACT: The diuretic bumetanide, which acts by blocking the Na-K-Cl cotransporter (NKCC), is widely used to inhibit neuronal NKCC1, particularly when NKCC1 expression is abnormally increased in brain diseases such as epilepsy. However, bumetanide poorly penetrates into the brain and, in rodents, is rapidly eliminated because of extensive oxidation of its N-butyl sidechain, reducing the translational value of rodent experiments. Inhibition of oxidation by piperonyl butoxide (PBO) has previously been reported to increase the half-life and diuretic activity of bumetanide in rats. Here we studied whether inhibition of bumetanide metabolism by PBO also increases brain levels of bumetanide in rats, and whether this alters pharmacodynamic effects in the kindling model of epilepsy. Furthermore, we studied the effects of PBO in mice. Mice eliminated bumetanide less rapidly than rats (elimination half-life 47 min vs. 13 min). Pretreatment with PBO increased the half-life in mice to average values (70 min) previously determined in humans, and markedly elevated brain levels of bumetanide. In rats, the increase in plasma and brain levels of bumetanide by PBO was less marked than in mice. PBO significantly increased the diuretic activity of bumetanide in rats and, less effectively, in mice. In epileptic mice, bumetanide (with PBO) did not suppress spontaneous seizures. In the rat kindling model, bumetanide (with or without PBO) did not exert anticonvulsant effects on fully kindled seizures, but dose-dependently altered kindling development. These data indicate that PBO offers a simple means to enhance the translational properties of rodent experiments with bumetanide, particularly when using mice.European Journal of Neuroscience 11/2013; · 3.75 Impact Factor
Article: Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal(R) vet, Phenoleptil(R)) in dogs.[Show abstract] [Hide abstract]
ABSTRACT: In human medicine, adverse outcomes associated with switching between bioequivalent brand name and generic antiepileptic drug products is a subject of concern among clinicians. In veterinary medicine, epilepsy in dogs is usually treated with phenobarbital, either with the standard brand name formulation Luminal(R) or the veterinary products Luminal(R) vet and the generic formulation Phenoleptil(R). Luminal(R) and Luminal(R) vet are identical 100 mg tablet formulations, while Phenoleptil(R) is available in the form of 12.5 and 50 mg tablets. Following approval of Phenoleptil(R) for treatment of canine epilepsy, it was repeatedly reported by clinicians and dog owners that switching from Luminal(R) (human tablets) to Phenoleptil(R) in epileptic dogs, which were controlled by treatment with Luminal(R), induced recurrence of seizures. In the present study, we compared bioavailability of phenobarbital after single dose administration of Luminal(R) vet vs. Phenoleptil(R) with a crossover design in 8 healthy Beagle dogs. Both drugs were administered at a dose of 100 mg/dog, resulting in 8 mg/kg phenobarbital on average. Peak plasma concentrations (Cmax) following Luminal(R) vet vs. Phenoleptil(R) were about the same in most dogs (10.9 +/- 0.92 vs. 10.5 +/- 0.77 mug/ml), and only one dog showed noticeable lower concentrations after Phenoleptil(R) vs. Luminal(R) vet. Elimination half-life was about 50 h (50.3 +/- 3.1 vs. 52.9 +/- 2.8 h) without differences between the formulations. The relative bioavailability of the two products (Phenoleptil(R) vs. Luminal(R) vet.) was 0.98 +/- 0.031, indicating that both formulations resulted in about the same bioavailability. Overall, the two formulations did not differ significantly with respect to pharmacokinetic parameters when mean group parameters were compared. Thus, the reasons for the anecdotal reports, if true, that switching from the brand to the generic formulation of phenobarbital may lead to recurrence of seizures are obviously not related to a generally lower bioavailability of the generic formulation, although single dogs may exhibit lower plasma levels after the generic formulation that could be clinically meaningful.BMC Veterinary Research 10/2013; 9(1):202. · 1.86 Impact Factor
Article: Pilocarpine-induced epilepsy in mice alters seizure thresholds and the efficacy of antiepileptic drugs in the 6-Hertz psychomotor seizure model.[Show abstract] [Hide abstract]
ABSTRACT: The 6-Hz psychomotor seizure model in mice is increasingly been used as a model for differentiation of anticonvulsant activity during development of new antiepileptic drugs (AEDs). It was previously proposed as a useful model of AED-resistant seizures, but more recent data have cast doubt on this proposal. The aim of the present study was to determine whether performing the 6-Hz test not in normal but epileptic mice renders the 6-Hz test more resistant to AEDs. Furthermore, thresholds for induction of 6-Hz seizures, maximal electroshock seizures (MES) and pentylenetetrazole (PTZ) seizures were compared in normal and epileptic mice, using the pilocarpine model. Epileptic mice had a significantly lower threshold for induction of 6-Hz seizures and were more susceptible to PTZ, whereas the MES threshold was not altered. Unexpectedly, 6-Hz seizures were not more resistant to AEDs in epileptic vs. nonepileptic mice, but instead showed an increased sensitivity to the anticonvulsant effects of some AEDs, particularly levetiracetam. The anticonvulsant ED50 of levetiracetam in the 6-Hz test (using a 32mA stimulus) was 17.6mg/kg in nonepileptic mice, but only 1.5mg/kg in epileptic mice. The data indicate that the complex pathophysiological and functional alterations associated with epilepsy in mice may strikingly alter the sensitivity of acutely induced seizures to an AED.Epilepsy research 10/2013; · 2.48 Impact Factor
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ABSTRACT: Despite the introduction of over 15 third-generation anti-epileptic drugs, current medications fail to control seizures in 20-30% of patients. However, our understanding of the mechanisms mediating the development of epilepsy and the causes of drug resistance has grown substantially over the past decade, providing opportunities for the discovery and development of more efficacious anti-epileptic and anti-epileptogenic drugs. In this Review we discuss how previous preclinical models and clinical trial designs may have hampered the discovery of better treatments. We propose that future anti-epileptic drug development may be improved through a new joint endeavour between academia and the industry, through the identification and application of tools for new target-driven approaches, and through comparative preclinical proof-of-concept studies and innovative clinical trials designs.dressNature Reviews Drug Discovery 09/2013; · 33.08 Impact Factor
Article: The novel antiepileptic drug imepitoin compares favourably to other GABA-mimetic drugs in a seizure threshold model in mice and dogs.[Show abstract] [Hide abstract]
ABSTRACT: Recently, the imidazolinone derivative imepitoin has been approved for treatment of canine epilepsy. Imepitoin acts as a low-affinity partial agonist at the benzodiazepine (BZD) site of the GABAA receptor and is the first compound with such mechanism that has been developed as an antiepileptic drug (AED). This mechanism offers several advantages compared to full agonists, including less severe adverse effects and a lack of tolerance and dependence liability, which has been demonstrated in rodents, dogs, and nonhuman primates. In clinical trials in epileptic dogs, imepitoin was shown to be an effective and safe AED. Recently, seizures in dogs have been proposed as a translational platform for human therapeutic trials on new epilepsy treatments. In the present study, we compared the anticonvulsant efficacy of imepitoin, phenobarbital and the high-affinity partial BZD agonist abecarnil in the timed i.v. pentylenetetrazole (PTZ) seizure threshold test in dogs and, for comparison, in mice. Furthermore, adverse effects of treatments were compared in both species. All drugs dose-dependently increased the PTZ threshold in both species, but anticonvulsant efficacy was higher in dogs than mice. At the doses selected for this study, imepitoin was slightly less potent than phenobarbital in increasing seizure threshold, but markedly more tolerable in both species. Effective doses of imepitoin in the PTZ seizure model were in the same range as those suppressing spontaneous recurrent seizures in epileptic dogs. The study demonstrates that low-affinity partial agonists at the benzodiazepine site of the GABAA receptor, such as imepitoin, offer advantages as a new category of AEDs.Pharmacological Research 09/2013; · 4.35 Impact Factor
Article: Pharmacological blockade of IL-1β/IL-1 receptor type 1 axis during epileptogenesis provides neuroprotection in two rat models of temporal lobe epilepsy.[Show abstract] [Hide abstract]
ABSTRACT: We studied whether pharmacological blockade of the IL-1β-mediated signaling, rapidly activated in forebrain by epileptogenic injuries, affords neuroprotection in two different rat models of status epilepticus (SE). As secondary outcome, we measured treatment's effect on SE-induced epileptogenesis. IL-1β signaling was blocked by systemic administration of two antiinflammatory drugs, namely human recombinant IL-1 receptor antagonist (anakinra), the naturally occurring and clinically used competitive IL-1 receptor type 1 antagonist, and VX-765 a specific non-peptide inhibitor of IL-1β cleavage and release. Antiinflammatory drugs were given 60min after antiepileptic (AED) drug-controlled SE induced by pilocarpine, or 180min after unrestrained electrical SE, for 7days using a protocol yielding therapeutic drug levels in brain. This drug combination significantly decreased both IL-1β expression in astrocytes and cell loss in rat forebrain. Neuroprotection and the antiinflammatory effect were more pronounced in the electrical SE model. Onset of epilepsy, and frequency and duration of seizures 3months after electrical SE were not significantly modified. Transcriptomic analysis in the hippocampus showed that the combined treatment did not affect the broad inflammatory response induced by SE during epileptogenesis. In particular, the treatment did not prevent the induction of the complement system and Toll-like receptors, both contributing to cell loss and seizure generation. We conclude that the IL-1β signaling represents an important target for reducing cell loss after SE. The data highlight a new class of clinically tested agents affording neuroprotection after a delayed post-injury intervention. Earlier blockade of this rapid onset inflammatory pathway during SE, or concomitant treatment with antiinflammatory drugs targeting additional components of the broad inflammatory response to SE, or co-treatment with AEDs, is likely to be required for optimizing beneficial outcomes.Neurobiology of Disease 08/2013; · 5.62 Impact Factor
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ABSTRACT: Several preclinical proof-of-concept studies have provided evidence for positive treatment effects on epileptogenesis. However, none of these hypothetical treatments has advanced to the clinic. The experience in other fields of neurology such as stroke, Alzheimer's disease, or amyotrophic lateral sclerosis has indicated several problems in the design of preclinical studies, which likely contribute to failures in translating the positive preclinical data to the clinic. The Working Group on "Issues related to development of antiepileptogenic therapies" of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) has considered the possible problems that arise when moving from proof-of-concept antiepileptogenesis (AEG) studies to preclinical AEG trials, and eventually to clinical AEG trials. This article summarizes the discussions and provides recommendations on how to design a preclinical AEG monotherapy trial in adult animals. We specifically address study design, animal and model selection, number of studies needed, issues related to administration of the treatment, outcome measures, statistics, and reporting. In addition, we give recommendations for future actions to advance the preclinical AEG testing.Epilepsia 08/2013; 54 Suppl 4:35-43. · 3.96 Impact Factor
Article: (R)-[(11)C]verapamil is selectively transported by murine and human P-glycoprotein at the blood-brain barrier, and not by MRP1 and BCRP.[Show abstract] [Hide abstract]
ABSTRACT: Positron emission tomography (PET) with [(11)C]verapamil, either in racemic form or in form of the (R)-enantiomer, has been used to measure the functional activity of the adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (Pgp) at the blood-brain barrier (BBB). There is some evidence in literature that verapamil inhibits two other ABC transporters expressed at the BBB, i.e. multidrug resistance protein 1 (MRP1) and breast cancer resistance protein (BCRP). However, previous data were obtained with micromolar concentrations of verapamil and do not necessarily reflect the transporter selectivity of verapamil at nanomolar concentrations, which are relevant for PET experiments. The aim of this study was to assess the selectivity of verapamil, in nanomolar concentrations, for Pgp over MRP1 and BCRP. Concentration equilibrium transport assays were performed with [(3)H]verapamil (5nM) in cell lines expressing murine or human Pgp, human MRP1, and murine Bcrp1 or human BCRP. Paired PET scans were performed with (R)-[(11)C]verapamil in female FVB/N (wild-type), Mrp1((-/-)), Mdr1a/b((-/-)), Bcrp1((-/-)) and Mdr1a/b((-/-))Bcrp1((-/-)) mice, before and after Pgp inhibition with 15mg/kg tariquidar. In vitro transport experiments exclusively showed directed transport of [(3)H]verapamil in Mdr1a- and MDR1-overexpressing cells which could be inhibited by tariquidar (0.5μM). In PET scans acquired before tariquidar administration, brain-to-blood ratio (Kb,brain) of (R)-[(11)C]verapamil was low in wild-type (1.3±0.1), Mrp1((-/-)) (1.4±0.1) and Bcrp1((-/-)) mice (1.8±0.1) and high in Mdr1a/b((-/-)) (6.9±0.8) and Mdr1a/b((-/-))Bcrp1((-/-)) mice (7.9±0.5). In PET scans after tariquidar administration, Kb,brain was significantly increased in Pgp-expressing mice (wild-type: 5.0±0.3-fold, Mrp1((-/-)): 3.2±0.6-fold, Bcrp1((-/-)): 4.3±0.1-fold) but not in Pgp knockout mice (Mdr1a/b((-/-)) and Mdr1a/b((-/-))Bcrp1((-/-))). Our combined in vitro and in vivo data demonstrate that verapamil, in nanomolar concentrations, is selectively transported by Pgp and not by MRP1 and BCRP at the BBB, which supports the use of (R)-[(11)C]verapamil or racemic [(11)C]verapamil as PET tracers of cerebral Pgp function.Nuclear Medicine and Biology 07/2013; · 2.52 Impact Factor
Article: Assessment of cerebral P-glycoprotein expression and function with PET by combined [(11)C]inhibitor and [(11)C]substrate scans in rats.[Show abstract] [Hide abstract]
ABSTRACT: INTRODUCTION: The adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (Pgp) protects the brain from accumulation of lipophilic compounds by active efflux transport across the blood-brain barrier. Changes in Pgp function/expression may occur in neurological disorders, such as epilepsy, Alzheimer's or Parkinson's disease. In this work we investigated the suitability of the radiolabeled Pgp inhibitors [(11)C]elacridar and [(11)C]tariquidar to visualize Pgp density in rat brain with PET. METHODS: Rats underwent a first PET scan with [(11)C]elacridar (n=5) or [(11)C]tariquidar (n=6) followed by a second scan with the Pgp substrate (R)-[(11)C]verapamil after administration of unlabeled tariquidar at a dose which half-maximally inhibits cerebral Pgp (3mg/kg). Compartmental modeling using an arterial input function and Logan graphical analysis were used to estimate rate constants and volumes of distribution (VT) of radiotracers in different brain regions. RESULTS: Brain PET signals of [(11)C]elacridar and [(11)C]tariquidar were very low (~0.5 standardized uptake value, SUV). There was a significant negative correlation between VT and K1 (i.e. influx rate constant from plasma into brain) values of [(11)C]elacridar or [(11)C]tariquidar and VT and K1 values of (R)-[(11)C]verapamil in different brain regions which was consistent with binding of [(11)C]inhibitors to Pgp and efflux of (R)-[(11)C]verapamil by Pgp. CONCLUSION: The small Pgp binding signals obtained with [(11)C]elacridar and [(11)C]tariquidar limit the applicability of these tracers to measure cerebral Pgp density. PET tracers with higher (i.e. subnanomolar) binding affinities will be needed to visualize the low density of Pgp in brain.Nuclear Medicine and Biology 06/2013; · 2.52 Impact Factor
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ABSTRACT: PURPOSE: In humans, traumatic brain injury (TBI) is one of the most common causes of acquired (symptomatic) epilepsy, but as yet there is no treatment to prevent the development of epilepsy after TBI. Animal models of posttraumatic epilepsy (PTE) are important to characterize epileptogenic mechanisms of TBI and to identify clinically effective antiepileptogenic treatments. The prevalence and phenomenology of naturally occurring canine epilepsy are similar to those in human epilepsy. However, the risk of epilepsy after TBI has not been systemically studied in dogs. We therefore performed a large retrospective study in 1,000 dogs referred to our clinical department over a period of 11.5 years with the aim to determine the incidence of early and late seizures after head trauma in this species. METHODS: Two strategies were used: in group I (n = 392), we evaluated whether dogs referred for the treatment of a head trauma (group Ia) or other trauma (group Ib) developed seizures after the trauma, whereas in group II (n = 608) we evaluated whether dogs referred for the treatment of recurrent epileptic seizures had a history of head trauma. Data for this study were obtained from our clinical database, questionnaires sent to the dogs' owners, and owner interviews. KEY FINDINGS: In group Ia, 6.6% of the dogs developed PTE, which was significantly different from group Ib (1.9%), indicating that head trauma increased the risk of developing epilepsy by a factor of 3.4. The risk of PTE increased with severity of TBI; 14.3% of the dogs with skull fracture developed PTE. In group II, 15.5% of the dogs with epilepsy had a history of head injury, which was significantly higher than the incidence of PTE determined for group Ia. SIGNIFICANCE: Our study indicates that head trauma in dogs is associated with a significant risk of developing epilepsy. Therefore, dogs with severe TBI are an interesting natural model of PTE that provides a novel translational platform for studies on human PTE.Epilepsia 01/2013; · 3.96 Impact Factor
Top Journals
University of Veterinary Medicine Hannover
Hanover, Lower Saxony, Germany
- Institute of Pathology
University of ZurichZürich, Zurich, Switzerland
University of Hamburg
Hamburg, Hamburg, Germany
- Department of Anaesthesiology
University of Eastern Finland
Kuopio, Eastern Finland Province, Finland
- A.I. Virtanen Institute for Molecular Sciences
The Scripps Research Institute
La Jolla, CA, United States
- Department of Cell and Molecular Biology
AIT Austrian Institute of Technology
Wien, Vienna, Austria
- Department of Health & Environment
University of Vienna
Vienna, Vienna, Austria
- Department of Medicinal Chemistry
Ludwig-Maximilians-University of MunichMünchen, Bavaria, Germany
Medical University of Vienna
Vienna, Vienna, Austria
- Universitätsklinik für Klinische Pharmakologie
Forschungszentrum Jülich
Düren, North Rhine-Westphalia, Germany
- Institut für Neurowissenschaften und Medizin (INM)
University of MünsterMuenster, North Rhine-Westphalia, Germany
National Institutes of Health
Bethesda, MD, United States
- Division of Epilepsy Research
Universität BremenBremen, Bremen, Germany
Hannover Medical School
Hannover, Lower Saxony, Germany
- Institute for Cellular and Molecular Pathology
The Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania, United States
University of Bonn
Bonn, North Rhine-Westphalia, Germany
- Epileptologische Klinik
Agricultural University in LublinLyublin, Lublin Voivodeship, Poland
Historisches Museum HannoverHanover, Lower Saxony, Germany
Copenhagen, Capital Region, Denmark
- Department of Neurology
Universität Bern
Bern, BE, Switzerland
- Laboratory for Dendrogeomorphology
Freie Universität Berlin
Berlin, Land Berlin, Germany
- • Institute of Pharmacology and Toxicology
- • Department of Veterinary Medicine


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All quotes tagged Natures
(4765 quotes found)
"A political convention is not a place where you can come away with any trace of faith in human nature."
"I cannot blame someone else for treachery, low moral living or thoughtless living, because they are like you, with different way of life, there is no escaping the human nature, is there?"
"Not only was it a good method that was effective and natural, but it really had a profound effect on the way we communicated about sexuality."
"No one on this earth is perfect. Every scar on my body is proof of every mistake I've ever made. However, mistakes don't make you stupid, not at all. Mistakes make you, you. They make you become more perfect at being you. So by all means, keep making mistakes, but not intentionally."