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Shower. Thursday , December 07th , 2017 - 18:58:19 PM
Perhaps, the most important thing to remember, when looking to buy a new shower stall, is the amount of space that you have available. If you are going from one bathtub to a bathtub and a standalone shower, there is a chance that you may be limited on space. If that is the case, you may find your options to be somewhat limited. That is unless you are planning on remodelling your entire bathroom. If you are planning on changing your entire bathroom around, it may be easier for you to find and purchase the shower stall of your choice, without having to worry about whether or not it will even fit in your bathroom.
If you have a custom shower (with multiple jets), a pressure balance valve is not a high flow valve, and cannot be expected to replace a thermostatic temperature control valve, especially in a multiple shower outlet installation. If the number of shower outlets desired is more than one valve can accommodate, it will be necessary to use two (or more) thermostat valves.
Best Shower Filter: Powerful, affordable and easy installation are said to be the middle name of the best shower filter available in the market. Choosing the best shower filter makes sure that you always get the clean and safe bath, so that you can enjoy your shower at the time of severe summers.
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This is a free online game and part of UNSORTED GAMES and his was played 31 times.In this free online game , you'll dress wild animals at the zoo . After you've clicked the button START GAME , you will be able to choose the cutest pet tie . Your mission will be to dress more suitable pet choice. To the right of the game screen you may notice that you can access Panola use to accomplish missions. The first enhancement is the cap , glasses second , third clothing , unique accessories fourth and last is to change the image back . After you have managed to combine acccesorii and got something you like then you can click on the button on the left which is like a camera, then you can print out the desired picture .
Use the mouse for all operations of the game.
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The HAPPY CUTE ZOO is a free online game was added on: by Hopystein and he is a 726-th online game on tihs onlne game website Hopystein. You can find more similar games on this category UNSORTED GAMES. After play this game got Rated 0 of 5 stars based on 0 players reviews . If you like this free game please share to you friends
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- by Thomas J.
- – on
- in Entertainment
As society has become obsessed with image, the fitness industry has boomed. This is no coincidence. The advancement of technology has brought with it revolutionary social media platforms that allow fitness models to show off their bodies and methods that led to their perfect self-made sculptures. Old-school fitness gurus would have to rely on word of mouth and pictures in order to spread their success. Nowadays, models can upload a picture of their body, nutrition advice, and workout tips in a matter of seconds. People want to emulate these figures, and what better way than to follow on social media and try to replicate their success?
Fitness models like Jen Selter, Michelle Lewin and Paige Hathaway have become famous through Instagram and Facebook, coining the term "Insta-famous." They've gotten big in the fitness industry by doing what they love and looking good doing it. Women want to know how these ladies transformed their bodies to near perfection, and guys, well; guys don't mind looking at them.
Ms. Selter and Ms. Lewin have become synonymous with looking like Greek Goddesses, but they're not the only ones you should be following for fitness advice. Gentlemen, if you want to look at some sick abs, toned legs or a perfect bum, you should follow these 15 women on social media in addition to the more famous sexy fitness gurus.
15 Katya Elise Henry
With almost 2.5 million followers (we don't know how many of those followers are angry tweens thanks to her relationship with singer Austin Mahone), Katya has a very loyal following and a very round and tight butt. She is a fitness model who lifts heavy weights in order to maintain her physique. Currently an ambassador for EHP Labs, Katya has become a personal trainer since graduating college, even implementing her own workout program.
She has become sort-of "insta-famous" thanks to her plump derriere, even catching the attention of celebrities. Her Instagram consists mostly of pictures of her posing and working out (with an occasional meal here and there), but are you complaining?
14 Karina Elle Lisenbee
Karina Elle Lisenbee is a 26-year old fitness trainer, model and former cheerleader who was named most In-Demand Fitness Model of 2014 by Racked Magazine. She became a model thanks to her statuesque figure and beautiful looks; she is 5'11" and a mix of Viatnemese and French. The former Florida Gator now dates gigantic pro bodybuilder Calum Von Moger, so you know those kids are going to be ginormous, fit and attractive.
In 2014, Lisenbee attempted to use her fitness background to her advantage and actually tried out for the WWE to become the next Diva. The beauty from Florida seems to be doing OK for herself as her website offers nutrition and training guides.
13 Jackie Perez
An avid Crossfitter, the 32-year old Jackie Perez looks a lot younger than her age implies. Ms. Perez is a lead trainer at Crossfit CSA, one of the most competitive Crossfit Gyms on the West Coast. The former collegiate volleyball player competed in the Reebok Crossfit Games from 2010-2012.
Thanks to her constant social media pictures showing off her toned derriere, Jackie is now sponsored by WFit, Savage Swim Bikinis and FitAid, amongst others. Aside from her booty shorts pictures (who's complaining?), Ms. Perez does post about her meals and her struggles and successes throughout her nutrition journey. You can even follow her on Snapchat and live through her daily chronicles. Her followers can resonate with her as she is very personable, honest and outgoing.
12 Michelle Lou Lan
Ms. Lou Lan, a former dancer who wisely brands herself "Meshyoga" in the world of social media, is the creator of her own successful yoga practice called "Mesh Yoga." She's been teaching yoga for almost ten years, and has created her own style of yoga that's simple and easy for newcomers to catch on. Her studio is located in Maui, Hawaii. She even has her own line of yoga clothing available to purchase on her website.
Judging by her Instagram pictures, she keeps herself in phenomenal shape. Many pictures show the exotic beauty in various yoga positions, so you can tell she definitely practices what she teaches.
11 Katy Hearn
Thanks to her own success and client transformations, this blue-eyed beauty has developed an enormous following on Instagram of over 1 million loyal people. While most males will not complain about her bikini pics, she mostly posts pictures and videos of her working out at the gym (and her dog, too. She loves that dog!). She has transformed herself over the years, and in doing so, has established believers and more clients. A decent amount of her pictures are devoted to her clients' own transformations who strive to look like Ms. Hearn one day. If that isn't good enough, then you can see her clients' results (along with some other good nutrition information) at her website.
10 Nochtli Peralta Alvarez
This former police officer turned fitness model (Imagine getting arrested by her, right? "Do you know why I pulled you over? No, but do it more often.") is a Dutch model of Mexican descent. Her unique look has turned heads in the modelling industry, and now she is using those looks to pursue her passion of fitness. Ms. Peralta Alvarez seems very down-to-Earth and approachable on her Instagram. She's sponsored by Body Engineers and devotes most of her recent social media posts to pictures of her modeling. Occasionally, she'll post about her nutrition and workouts, but one look at those bright green eyes and you're drawn to her page.
9 Mattie Rogers
You might recognize Mattie Rogers from her infamous Olympic lifting fail from March 2016, but what you might not know is Mattie holds eight American records in her weight class. She's only 20 years old! And she's beautiful. Ms. Rogers is strong as hell, evidenced by her numerous videos on her Instagram displaying her lifting more than most men I know. She has no shame, showing pictures and videos of her failing her lifts, messing around in her spare time, or just being her ridiculous self. Although she did not qualify for the USA Olympics, I'm sure this is not the last time we'll see Maddie strutting her stuff. I sure hope not.
Featured Today
8 Julia Gilas
Move over, Jen Selter. You have a new challenger for best butt these days. Julia Gilas is all over Instagram, and it seems like she is sponsored by everybody. Half of her pictures and videos are of her posing in bathing suits and tight-fitting gym clothes, and the other half of her pictures advertise "Fit Tea" or "Sweet Sweat" products. The companies know what they're doing as potential consumers will see Julia Gilas in booty shorts rocking some tea products, and those who want to look as good as Ms. Gilas does will become buyers (she also handles personalized diets through her website). Whatever she does use is definitely working.
7 TIE: Natasha Oakley and Devin Brugman
It's technically cheating putting these two as one, but if you follow either one on Instagram, you realize they're nearly inseparable. These two BFFs have created "A Bikini a Day," "Monday Swimwear" and "Monday Active," the latter company devoted to fitness. They've formed "Monday Active" targeted towards females to wear clothing at the gym and throughout the day. These two models have kept busy promoting their new clothing line and have instituted a new series devoted to fitness: the 2016 Bikini a Day #Bodylove Fitness Series. Known for their good looks and figures, these two supermodels are proving they're more than pretty faces.
6 Arianny Celeste
Best known for her work as a UFC Ring Girl, Arianny Celeste is probably the most recognizable fitness guru on this list. This beautiful self-proclaimed "fitness nerd" isn't afraid of flaunting her perfect figure. The former dancer graduated from UNLV with a degree in Fitness Management and Nutrition and maintains her knowledge through blogging. Thanks to her good looks and fame, Arianny has a few sponsors and frequently posts about how she stays in shape thanks to "Protein world." Ms. Celeste also has a penchant for travelling as she's been modelling lately across different exotic locations. She's living proof that a fitness background can be a great stepping stone towards success.
5 Kristen Maynard
For those familiar with "Morellifit," Kristen Maynard immediately stands out as the most beautiful of the personal trainers/nutrition experts that works for the extremely successful and ever-growing company. The extremely humble Ms. Maynard is a coach at Morellifit and has conquered her own demons by beating an eating disorder.
She's in the gym every day, and you can follow her narrative on Instagram. Freqently posting progress pictures and inspirational quotes, the Phoenix Resident also participates in fitness competitions. She's now a nutrition expert and based on overcoming her own adversities, she has become the perfect fitness guru to follow on Instagram.
4 Ana Cheri
With an astounding 6.3 million followers on Instagram, Ana Cheri has made a huge name for herself. Her ethnic look and phenomenal build have allowed her to become a superstar in the fitness industry. The California Beauty works for Shredz and has recently opened her own gym called "Be More Athletics" in Santa Ana, California.
When she is not posting shots of her butt and amazing curves on Instagram for her fans, she participates in bikini competitions. Her success in the fitness world has given her the ability to create a brand. She now sells merchandise and calendars on her website.
3 Alice Matos
The top four hottest fitness gurus are separated only by the slightest of margins. Alice Matos has created such a loyal following on social media that her own fan club has over 5,200 followers In addition to a loyal fan base, Matos has a nearly flawless figure (#abs). No matter what she's wearing or doing in her pictures, one thing remains evident: Matos looks good and fit doing it.
The fitness superstar has created her own clothing line called "La Bella Mafia" geared towards working out, being comfortable and hoping to look as good as Matos in doing so.
2 Anllela Sagra
This 22-year old former model is now a 1Up Nutrition Athlete. Her dream of becoming Columbia's first fitness model gave her the drive to transform herself from a thin model to the current fitness beauty we see today. While her 4.7 million followers witness her working out and playing around and posing in her bikini, Ms. Sagra does take great pride in assisting her followers. She regularly holds transformation programs that she advertises on Instagram and tracks on her website. Potential clients can participate in a variety of programs geared towards specific goals (Ab Ripper, Booty Blaster) or can have a meal plan engineered on their behalf.
1 Karina Irby
Karina Irby has become incredibly successful in her home country of Australia, and based on her figure, she should be even more successful across the globe. She started her own bathing suit company called Moana Bikini, and her success spread like wildfire. Now that she has become a huge hit, Ms. Irby has created Bikini Body Burn filled with many fitness challenges that prove she's no joke in the working out department. She promotes a healthy lifestyle utilizing the Bikini Body Burn Instagram Account, showing pictures and videos of her working out, her fitness programs, her meals, client's transformations, and last, but definitely not least, her perfect booty.
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Access Office Industries resellers / account customers. It is not available to
the general public.
Access Office Industries resellers / account customers. It is not available to
the general public.
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If Flexibility is a key metric for your office then you will be excited by the Eclipse® Prism range of Workstation Frames and Workstation furniture. The Eclipse® Prism range is an extremely popular integrated design of workstation that allows maximum configurations and minimal hassle, Sure to meet the needs of a demanding modern day work force
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client testimonials
The Campaspe Regional Library Echuca officially opened on August 24, 2012. There are many stunning aspects within this facility, one of which is our wonderful shelving supplied by Eclipse Commercial Furniture. A range of mobile and static shelving provide the flexibility we were after, as well as incorporating face out shelving which helps promote our collection. The custom designed DVD, Audio and Picture book shelving work particularly well as they are easy for the customers to use as well as being appealing pieces of furniture. The slat wall bay panels colour and design complement the rest of the library's interior colours. The addition of iPad holders have proved to be a popular and very workable alternative to the traditional bay end opac. Access Office also provided a number of lap top tables which are terrific and are placed all through out the library. We are exceptionally pleased with the end result and thank Eclipse Commercial Furniture for completing this part of the project for us and for addressing any problems that arose during the installation.< /p>
Campaspe Regional Library Echuca , Echuca
Hi Jamie, Thank you for doing such a great job with the supply of furniture at Bullsbrook. I was there this morning and it looks great Thank you. Kind regards, Julie-Anne
Ethel Warren Bullsbrook Community Centre & Library,
Hello I just wanted to say thank you for the very speedy service and ease of purchasing. My ottomans were delivered and within about 15 minutes of me unwrapping them they were in full use, and all the other staff are very jealous! Thanks again. Kindest regards Shelley Antoni
St Paul's Primary School Library,
Hi Errol "Many thanks for the smooth delivery and installation of our furniture. We are especially grateful to Carl who went above and beyond the last couple of days." Ghylène Palmer Senior Librarian - Mount Lawley & Bunbury Campus Libraries
Just a quick note to say thank you for the safe delivery of the furniture. We have installed them in the library and I would have to say that the children are very excited. I had to limit the amount of time that they could sit on the yellow tub chairs so that everyone could have a turn. It was quite entertaining to watch.
St Mary's Primary School, Sydney
Good morning gents I wanted to thank you for all your advice, guidance and services this year and to share a few photos with you. Our first exams are underway and the students are experiencing this in our very first set up in the 3 sports halls. Sports hall 1 and 2 are the largest halls, and i think you will agree it looks amazing. We are so excited and relieved and im sure you will understand this feeling. Thank you again, Karen, Manager, Quality and Services Delivery Facilities and Services Centre - Edith Cowan University
ECU Joondalup ,
A nice word from Procurement at SJG (St John of God - Health Care) You're marvellous Geoff Thank You John Warren, Group Manager, Supply Logistics and Project Capital Equipment Procurement Group Services WA
St John of God - Health Care, Midland
Dear Errol Our new furniture is lovely. Thanks very much for your care and assistance as well as that of your marvellous team. James and the hard working gentlemen (Peter, Gary and John) who did such a great job of the deliveries.The y worked quickly, efficiently and were very polite and helpful. Many Thanks
Balcatta Senior High School, Balcatta
Wow the units look amazing, the teachers are extremely happy with the resul t. K ind regards Michelle West Greenwood Primary School
West Greenwood Primary School,
Thank-you very much for your service and help with our library shelves. They look good in our new building now we just have to get the finishing touches done on the building and we can start to move our books across and set up our library. The Pingrup CRC look forward to having many years of use of our new shelving.Thank -you and your company once again for the service and won't hesitate in recommending you to other organizations.
Pingrup Community Resource Centre, Pingrup


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Join us for our August Advanced Asana workshop. Learn how to wisely and effectively work toward Firefly Pose or refine your work in this challenging arm balance. Enjoy Andrea's great instruction and encouragement, knowing that each person can modify according to his or her needs - preparation is a big part of the fun and challenge.
You'll have time to warm up, cool down, and discover how and why this pose can help you express freedom and radiance.
Yoga experience strongly suggested – students should be confident in their ability in a Yoga Bird Flow class.


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Brussels (BRU) to Halifax (YHZ) flights from EUR 371*
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Pharmacist in meningitis outbreak gets 8 years in prison
BOSTON (AP) — A Massachusetts pharmacist convicted for his role in a deadly 2012 meningitis outbreak fought through sobs as he apologized to victims and their families Wednesday before being sentenced to eight years in prison.
Nearly 80 people died and almost 800 were sickened in what's considered the worst public health crisis in recent U.S. history. The fungal meningitis outbreak was caused by mold-tainted steroid injections produced by the New England Compounding Center.
Glen Chinn, who ran the so-called clean rooms where the drugs were made, sobbed as he struggled through his statement during his sentencing hearing in Boston's federal courthouse. Chin said he knows some victims will never forgive him, but he'll continue to pray that they will find some sort of peace.
"I realize these are just words and nothing will bring back your loved ones," the 49-year-old said, occasionally turning to look directly at the victims and their relatives seated behind him. "But believe me when I say that I am truly sorry that this ever occurred," he said.
Prosecutors wanted a 35-year-sentence for Chin, pointing to the devastating impact the outbreak had on families across the country. Chin's lawyers asked for about three years behind bars.
Assistant U.S. Attorney Amanda Strachan relayed how a victim's daughter said she heard her mother's scream of pain from floors below when the daughter visited her mother in the hospital. The daughter compared the sound of her mother's screams to the sound of the ship careening into the ocean in the movie "Titanic," Strachan said.
"That's the sound that she has in her head when she thinks about her mother's death," Strachan said. "It's the sound made by Glenn Chin's conduct."
Mary Beth Krakowski of South Bend, Indiana, whose aunt died at age 88 after being injected with the contaminated drugs, told Chin he had a chance to be a "hero" and blow the whistle on the pharmacy's dangerous practices.
"How did you get lost? How did you lose those ideals? How could you have fallen so far to become uncaring, cold and callous enough to put the patients' welfare behind your personal gain?" asked Krakowski, the niece of Alice Machowiak.
Chin was convicted in October of racketeering and mail fraud but was cleared of second-degree murder, which could have brought a life sentence. He had had been charged with the deaths of 25 people in Florida, Indiana, Maryland, Michigan, North Carolina, Tennessee and Virginia.
Throughout his trial, prosecutors portrayed him as a callous employee who cut corners and ignored warning signs of unsafe production methods to boost production and profits.
Chin's attorneys argued that he didn't deserve more time behind bars than the pharmacy's co-founder, Barry Cadden, who's serving a nine-year sentence for his role in the outbreak. Cadden also was acquitted of second-degree murder.
Chin's attorneys said Cadden was the one calling the shots and that Chin just couldn't stand up to his boss. They said there was no evidence Chin caused the drugs to become contaminated.
"There is more to Glenn Chin than NECC," attorney Stephen Weymouth told the judge, pointing to the dozens of letters written by friends and family that described him as a mentor and loving father to his two young children.
"This will be Glenn Chin's own prison from which he will never be able to get out of for as long as he lives," Weymouth said.
After the sentencing, victims expressed their dismay at what they considered to be a light sentence and the fact that neither Chin nor Cadden were convicted of murder.
"I want somebody in there blamed for the deaths," said Willard Mazure, Jr., of Michigan, who became sickened after receiving an injection in 2012. "We've got 80 people dead, and nobody is responsible."
The judge ordered Chin to report to prison in March.
Follow Alanna Durkin Richer @aedurkinricher . Read more of her work here .
The cambodian cure for resistant scabies mites
A member shares his story in how he was cured from resistant scabies mites in Cambodia. Where ivermectin and permethrin failed a local monk in a small town in Cambodia combated it with natural herbs and ancient remedies
Facebook group: Human Parasites Support Network
New Lyme disease tests could offer quicker, more accurate detection
New tests to detect early Lyme disease — which is increasing beyond the summer months -could replace existing tests that often do not clearly identify the infection before health problems occur.
In an analysis published on December 7 in Clinical Infectious Diseases, scientists from Rutgers University, Harvard University, Yale University, National Institute of Allergy and Infectious Diseases of the NIH and other academic centers, industry and public health agencies say new diagnostic methods offer a better chance for more accurate detection of the infection from the Lyme bacteria.
"New tests are at hand that offer more accurate, less ambiguous test results that can yield actionable results in a timely fashion," said Steven Schutzer, a physician-scientist at Rutgers New Jersey Medical School and senior author. "Improved tests will allow for earlier diagnosis which should improve patient outcomes."
Lyme disease is the most common tick-borne infection in North America and Europe. There are currently over 300,000 cases of Lyme disease annually in the United States alone and the disease is increasing and spreading into new regions. Lyme disease frequently, but not always, presents with a bull's-eye rash. When the rash is absent, a laboratory test is needed.
The only FDA approved Lyme disease tests, based on technology developed more than two decades ago, rely on detecting antibodies that the body's immune system makes in response to the disease. These antibody-based tests are the most commonly used tests for Lyme disease and are the current standard.
One problem, however, is that many people produce similar — called "cross-reactive" — antibodies in response to other bacteria not associated with Lyme disease, which causes confusing results and makes test accuracy more difficult.
"New tests are more exact and are not as susceptible to the same false-positive or false-negative results associated with current tests," said Schutzer.
Schutzer and his colleagues say more accurate testing would help doctors decide when to prescribe the antibiotics used to clear the infection and help avoid severe long-term health problems. Antibody tests, can take three weeks or more for the antibody levels to reach a point where the tests can pick up a positive result.
Those involved in the paper joined forces after meeting at Cold Spring Harbor Laboratory's Banbury Center, a nonprofit research institution in New York. The meeting organized and chaired by Schutzer and John A. Branda, assistant professor of pathology at Harvard Medical School, focused on current Lyme disease tests and new scientific advances made in increasing the accuracy of the diagnosis.
"This meeting and paper resulting from it are particularly significant," said Jan Witkowski, professor in the Watson School of Biological Sciences at Cold Spring Harbor Laboratory who along with Nobel Laureate James Watson asked Schutzer to lead several symposia. "The participants noted that there are greatly improved diagnostic tests for Lyme disease that can be implemented now, and that the way is open to the development of further tests."
Story Source:
provided by Rutgers University. Original written by Robin Lally.
Journal Reference:
- John A Branda, Barbara A Body, Jeff Boyle, Bernard M Branson, Raymond J Dattwyler, Erol Fikrig, Noel J Gerald, Maria Gomes-Solecki, Martin Kintrup, Michel Ledizet, Andrew E Levin, Michael Lewinski, Lance A Liotta, Adriana Marques, Paul S Mead, Emmanuel F Mongodin, Segaran Pillai, Prasad Rao, William H Robinson, Kristian M Roth, Martin E Schriefer, Thomas Slezak, Jessica Snyder, Allen C Steere, Jan Witkowski, Susan J Wong, Steven E Schutzer. Advances in Serodiagnostic Testing for Lyme Disease Are at Hand. Clinical Infectious Diseases, 2017; DOI: 10.1093/cid/cix943
Possible new way to treat parasitic infections discovered
A chemical that suppresses the lethal form of a parasitic infection caused by roundworms that affects up to 100 million people and usually causes only mild symptoms has now been identified by researchers.
UT Southwestern Medical Center researchers have identified a chemical that suppresses the lethal form of a parasitic infection caused by roundworms that affects up to 100 million people and usually causes only mild symptoms.
"The approach we used could be applied generally to any nematode parasite, not just this one type," said Dr. David Mangelsdorf, Chair of Pharmacology, an Investigator in the Howard Hughes Medical Institute (HHMI), and one of three corresponding authors of the study published in the Proceedings of the National Academy of Sciences. The study's other corresponding authors are at two universities in Philadelphia.
"The plan is to develop better compounds that mimic the Δ7-dafachronic acid used in this study and eventually to treat the host to stop parasitic infection," he added.
The Centers for Disease Control and Prevention (CDC) reports that the soil-dwelling Strongyloides stercoralis nematode, or roundworm, is the primary strongyloides species that infects humans. Experts estimate that between 30 million and 100 million people are infected worldwide, and most of them are unaware of it because their symptoms are so mild. The parasite can persist for decades in the body because of the nematode's unique ability to reinfect the host, repeatedly going through the early stages of its life cycle. The nematode that causes the original infection exists in dirt on all continents except Antarctica, and it is most common in warmer regions, particularly remote rural areas in the tropics and subtropics where walking barefoot combined with poor sanitation leads to infection.
However, in people with compromised immune systems — such as those using long-term steroids for asthma, joint pain, or after an organ transplant — the mild form of the illness can progress to the potentially lethal form, a situation called hyperinfection. Studies indicate that mortality from untreated hyperinfection can be as high as 87 percent.
The World Health Organization reports that although the parasitic illness has almost disappeared in countries where sanitation has improved, children remain especially vulnerable in endemic regions due to their elevated contact with dirt. Further, the drug of choice, ivermectin, is unavailable in some affected countries.
"Ivermectin is used to treat the disease but is less effective in the lethal form of the infection," said Dr. Mangelsdorf, a Professor of Pharmacology and Biochemistry. "We do not know exactly how the glucocorticoid [steroid] causes hyperinfection, but once it does, ivermectin is much less effective, prompting the search for new drugs. The new drug we used in our mouse model appears to be very effective," he said.
To study the still unknown pathogenesis of the disease, the researchers developed a mouse model susceptible to the full range of infection by the human parasite. Because mice with intact immune systems are resistant to S. stercoralis infection, the researchers began with an immunocompromised strain of mice, and then exposed some to a synthetic steroid called methylprednisolone (MPA) that is commonly used to treat asthma in humans.
The mice were then exposed to the parasitic worms. Compared with untreated mice, those that received the steroid showed a tenfold increase in the number of parasitic female worms and a 50 percent increase in mortality, said Dr. Mangelsdorf, who holds both the Alfred G. Gilman Distinguished Chair in Pharmacology and the Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology in Honor of Harold B. Crasilneck, Ph.D.
In addition, third-stage larvae — the life cycle stage in which the worms can initiate hyperinfection — were found in higher numbers in the steroid-treated versus untreated mice, he added.
"Strikingly, treatment with a steroid hormone called Δ7-dafachronic acid, a chemical that binds to a parasite nuclear receptor called Ss-DAF-12, significantly reduced the worm burden in MPA-treated mice," Dr. Mangelsdorf said. The Ss-DAF-12 receptor corresponds to a similar receptor in the long-studied C. elegans worm.
Dr. Mangelsdorf and colleagues previously showed (PNAS, 2009) that the DAF-12 receptor pathway is found in many parasitic species. They also showed that activating the receptor with Δ7-dafachronic acid could override the parasite's development and prevent S. stercoralis from becoming infectious.
"Overall, this latest study provides a useful mouse model for S. stercoralis autoinfection and opens the possibility of new chemotherapy for hyperinfection by targeting the parasite's own steroid hormone mechanism," Dr. Mangelsdorf said.
Story Source:
provided by UT Southwestern Medical Center.
Journal Reference:
- John B. Patton, Sandra Bonne-Année, Jessica Deckman, Jessica A. Hess, April Torigian, Thomas J. Nolan, Zhu Wang, Steven A. Kliewer, Amy C. Durham, James J. Lee, Mark L. Eberhard, David J. Mangelsdorf, James B. Lok, David Abraham. Methylprednisolone acetate induces, and Δ7-dafachronic acid suppresses,Strongyloides stercoralishyperinfection in NSG mice. Proceedings of the National Academy of Sciences, 2018; 201712235 DOI: 10.1073/pnas.1712235114
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By Alex Avdeef
Of the loads of millions of compounds synthesized every year, such a lot have virtually no probability of changing into medications. This challenge exists simply because such a lot molecules lack the drug-like homes essential to allow them to be potent in vivo. to handle this factor, Alex Avdeef's Absorption and Drug improvement indicates the reader how one can study a compound's pharmaceutical houses, emphasizing oral absorption. This ebook explains the several physicochemical tools at present used to research drug applicants and the way to interpret those tools. additionally integrated are physicochemical facts for over 2 hundred advertisement medicines. With over six hundred references and a hundred drawings, this publication is a wonderful source for the sensible pharmaceutical chemist and people looking a greater realizing of physicochemical measurements.
Read or Download Absorption and Drug Development: Solubility, Permeability and Charge State PDF
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Additional resources for Absorption and Drug Development: Solubility, Permeability and Charge State
Sample text
One can estimate pKa values, intelligently guess the values of Ejk, and use these to calculate values of Aik. In the calculation, the objective is to minimize the sum of the residuals between the calculated and observed absorbances, S¼ species X spectraðpHÞ X k i calc 2 ðAobs ik À Aik Þ s2ik ð3:11Þ where sik are the estimated uncertainties in the measured values of absorbances. Mathematically imposed constraints prevent the calculation of negative values of absorbances [227]. The ''best'' set of refined pKa constants are those that minimize S.
Note that for the uncharged species, Eq. 3) takes on the form P0 ¼ Dm Kp h ð2:6Þ where Kp ¼ Cm ð0Þ=CD0 ; also, Kp ¼ Cm ðhÞ=CA0 ; CD0 and CA0 are the aqueous solution concentrations of the uncharged species in the donor and acceptor sides, respectively. , excess solid present) at some pH, the plot of log C0 versus pH for an ionizable molecule is extraordinarily simple in form; it is a combination of straight segments, joined at points of discontinuity indicating the boundary between the saturated state and the state of complete dissolution.
Unfortunately, a titration curve does not always reveal all the pKa values that a molecule may have. To reveal the other two pKa values of M6G and to test for overlapping pKa values, it is necessary to transform the titration curves into Bjerrum plots [112,116,118,153,163–165]. 1 Bjerrum Plots The Bjerrum plots are probably the most important graphical tools in the initial stages of titration data analysis. Since one knows how much strong acid and strong base have been added to the solution at any point and also how many dissociable protons the sample substance brings to the solution, one knows the total hydrogen ion concentration in solution, despite what equilibrium reactions are taking place.
Absorption and Drug Development: Solubility, Permeability and Charge State by Alex Avdeef
by Anthony


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