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December 2, 2014

Jonathan Tobin: Defending the Right to a Jewish State

Heather Hale: Compliment your kids without giving them big heads

Megan Shauri: 10 ways you are ruining your own happiness

Carolyn Bigda: 8 Best Dividend Stocks for 2015

Kiplinger's Personal Finance editors: 7 Things You Didn't Know About Paying Off Student Loans

Samantha Olson: The Crucial Mistake 55% Of Parents Are Making At Their Baby's Bedtime

Densie Well, Ph.D., R.D. Open your eyes to yellow vegetables

The Kosher Gourmet by Megan Gordon With its colorful cache of purples and oranges and reds, COLLARD GREEN SLAW is a marvelous mood booster --- not to mention just downright delish
April 18, 2014

Rabbi Yonason Goldson: Clarifying one of the greatest philosophical conundrums in theology

Caroline B. Glick: The disappearance of US will

Megan Wallgren: 10 things I've learned from my teenagers

Lizette Borreli: Green Tea Boosts Brain Power, May Help Treat Dementia

John Ericson: Trying hard to be 'positive' but never succeeding? Blame Your Brain

The Kosher Gourmet by Julie Rothman Almondy, flourless torta del re (Italian king's cake), has royal roots, is simple to make, . . . but devour it because it's simply delicious

April 14, 2014

Rabbi Dr Naftali Brawer: Passover frees us from the tyranny of time

Greg Crosby: Passing Over Religion

Eric Schulzke: First degree: How America really recovered from a murder epidemic

Georgia Lee: When love is not enough: Teaching your kids about the realities of adult relationships

Cameron Huddleston: Freebies for Your Lawn and Garden

Gordon Pape: How you can tell if your financial adviser is setting you up for potential ruin

Dana Dovey: Up to 500,000 people die each year from hepatitis C-related liver disease. New Treatment Has Over 90% Success Rate

Justin Caba: Eating Watermelon Can Help Control High Blood Pressure

The Kosher Gourmet by Joshua E. London and Lou Marmon Don't dare pass over these Pesach picks for Manischewitz!

April 11, 2014

Rabbi Hillel Goldberg: Silence is much more than golden

Caroline B. Glick: Forgetting freedom at Passover

Susan Swann: How to value a child for who he is, not just what he does

Cameron Huddleston: 7 Financial Tasks You Should Tackle Right Now

Sandra Block and Lisa Gerstner: How to Profit From Your Passion

Susan Scutti: A Simple Blood Test Might Soon Diagnose Cancer

Chris Weller: Have A Slow Metabolism? Let Science Speed It Up For You

The Kosher Gourmet by Diane Rossen Worthington Whitefish Terrine: A French take on gefilte fish

April 9, 2014

Jonathan Tobin: Why Did Kerry Lie About Israeli Blame?

Samuel G. Freedman: A resolution 70 years later for a father's unsettling legacy of ashes from Dachau

Jessica Ivins: A resolution 70 years later for a father's unsettling legacy of ashes from Dachau

Kim Giles: Asking for help is not weakness

Kathy Kristof and Barbara Hoch Marcus: 7 Great Growth Israeli Stocks

Matthew Mientka: How Beans, Peas, And Chickpeas Cleanse Bad Cholesterol and Lowers Risk of Heart Disease

Sabrina Bachai: 5 At-Home Treatments For Headaches

The Kosher Gourmet by Daniel Neman Have yourself a matzo ball: The secrets bubby never told you and recipes she could have never imagined

April 8, 2014

Lori Nawyn: At Your Wit's End and Back: Finding Peace

Susan B. Garland and Rachel L. Sheedy: Strategies Married Couples Can Use to Boost Benefits

David Muhlbaum: Smart Tax Deductions Non-Itemizers Can Claim

Jill Weisenberger, M.S., R.D.N., C.D.E : Before You Lose Your Mental Edge

Dana Dovey: Coffee Drinkers Rejoice! Your Cup Of Joe Can Prevent Death From Liver Disease

Chris Weller: Electric 'Thinking Cap' Puts Your Brain Power Into High Gear

The Kosher Gourmet by Marlene Parrish A gift of hazelnuts keeps giving --- for a variety of nutty recipes: Entree, side, soup, dessert

April 4, 2014

Rabbi David Gutterman: The Word for Nothing Means Everything

Charles Krauthammer: Kerry's folly, Chapter 3

Amy Peterson: A life of love: How to build lasting relationships with your children

John Ericson: Older Women: Save Your Heart, Prevent Stroke Don't Drink Diet

John Ericson: Why 50 million Americans will still have spring allergies after taking meds

Cameron Huddleston: Best and Worst Buys of April 2014

Stacy Rapacon: Great Mutual Funds for Young Investors

Sarah Boesveld: Teacher keeps promise to mail thousands of former students letters written by their past selves

The Kosher Gourmet by Sharon Thompson Anyone can make a salad, you say. But can they make a great salad? (SECRETS, TESTED TECHNIQUES + 4 RECIPES, INCLUDING DRESSINGS)

April 2, 2014

Paul Greenberg: Death and joy in the spring

Dan Barry: Should South Carolina Jews be forced to maintain this chimney built by Germans serving the Nazis?

Mayra Bitsko: Save me! An alien took over my child's personality

Frank Clayton: Get happy: 20 scientifically proven happiness activities

Susan Scutti: It's Genetic! Obesity and the 'Carb Breakdown' Gene

Lecia Bushak: Why Hand Sanitizer May Actually Harm Your Health

Stacy Rapacon: Great Funds You Can Own for $500 or Less

Cameron Huddleston: 7 Ways to Save on Home Decor

The Kosher Gourmet by Steve Petusevsky Exploring ingredients as edible-stuffed containers (TWO RECIPES + TIPS & TECHINQUES)

Jewish World Review

Venomous drugs: The pressure-drop viper

By James Mitchell Crow


Since cone snail venom shuts down the nervous system of prey, it may have great potential as a pain medication



The healing powers of toxins


JewishWorldReview.com | A brush with a pit viper is not a relaxing experience. These snakes are venomous, can grow to several meters long and will be on to you long before you know they're there, sensing your body heat with a pair of highly sensitive infrared-detecting organs that sit just below their eyes. Bumping into one of these creatures in their native forests in South America would not be good for anyone's heart, so it's ironic that pit viper venom has given us a drug used to treat high blood pressure.

In fact, the toxic mixtures of chemicals we call venoms have a long history as medical treatments. From poisonous toads to toxic tarantulas, venomous animals provide ingredients for traditional medicines around the world. Unlikely as it sounds, venoms have many of the attributes a good drug needs.

When a venomous animal pounces on its prey, the chemicals it injects must be stable enough to travel around the victim's body and able to evade its defenses until they reach their site of action, when they must hit the target with exquisite selectivity and minimum side effects. Millennia of evolution have honed venoms to achieve exactly what a doctor hopes an injected drug will do.

Nevertheless, Western medicine has had difficulties cashing in on this natural asset. In 1981, captopril, a drug based on pit viper venom, became the first venom-derived drug to be approved by the U.S. Food and Drug Administration. In the following two decades, pharmaceutical companies produced a slow trickle of other such drugs.

Now, this trickle looks set to turn into a steady stream as venom research enters the genomics age, turning the once-laborious job of sifting through toxic cocktails for potential cures into a high-throughput process. As a result, venom is one of the hottest commodities in pharmaceuticals. New Scientist surveys what it has to offer:

1. DRUG: Captopril

SOURCE: Pit viper

CONDITION: Hypertension



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How does deadly pit viper venom work as a drug? It's all a question of quantity.

"Every medicine is also a poison -- the effect depends on the dose," says Bryan Fry, who researches venomous animals and their evolution at the University of Queensland in Brisbane, Australia. "The snake kills by dropping its target's blood pressure through the floor," he says. "To use the venom as a drug, you just give less of it."

Pit viper venom provided more than just the original venom-based drug, though. It is also intimately tied up with the discovery of how the body regulates blood pressure. In the late 1960s, this mechanism was still something of a mystery, confounding efforts to manipulate it. Among those working to understand it was John Vane, a pharmacologist at the Royal College of Surgeons of England.

The breakthrough came when a Brazilian postdoctoral researcher, Sergio Ferreira, joined Vane's group. Ferreira had been studying the venom of a pit viper native to Brazil, Bothrops jararaca, and he brought a sample of it with him. The team discovered that a toxic peptide in the venom would selectively inhibit the action of angiotensin-converting enzyme (ACE), a chemical suspected of playing a role in the regulation of blood pressure.

During the following decade, the role of ACE in boosting blood pressure by controlling the release of water and salts from the kidneys became clear -- as did the therapeutic value of blocking it. Captopril, a synthetic analogue of the snake venom peptide, was first made in 1975, and hit the clinic just six years later. It was the founder member of what is now a family of ACE inhibitor drugs (Hypertension).

Most of the venom-derived drugs approved since captopril also originated in snakes, mainly because snake venoms are the easiest to work with. Compared with a scorpion or a spider, say, snakes produce a vast volume of venom, making them easier to analyze. Snake venom is also a much simpler cocktail than that produced by many other animals: A spider's venom can contain over 1,000 peptides, whereas a snake's venom might contain only 25.

2. DRUG: Chlorotoxin

SOURCE: Deathstalker scorpion

CONDITION: Cancer

Radioactive scorpion venom might sound like the stuff comic-book villains would use. In fact, it's an experimental anti-cancer drug in clinical trials. The venom in question comes from the deathstalker scorpion (Leiurus quinquestriatus), a bright yellow beast native to north Africa and the Middle East. As the name suggests, its sting can be fatal.

Within that sting lies a peptide called chlorotoxin, which has an unusual property -- it sticks strongly to tumor cells while ignoring surrounding healthy tissue, by binding to a cancer-specific protein called matrix metalloproteinase-2. This tumor-targeting makes it a promising ally in the fight against cancer.

Load up chlorotoxin with a radioisotope, for example, and it will deliver its radioactive payload straight to a tumor. This approach has been investigated by TransMolecular, a company based in Cambridge, Mass., as a way to treat glioma, a form of brain cancer. Chlorotoxin passed a phase II clinical trial in 2009.

More recently, the peptide has become the key ingredient in an experimental surgical tool called Tumor Paint. When chlorotoxin is tagged with a fluorescent dye, it will illuminate a tumor -- a trick that makes the surgeon's job easier by helping to pinpoint cancerous growth and ensure that all the cancerous cells are removed and healthy tissue spared.

Chlorotoxin's performance through the early stages of clinical trials has not gone unnoticed. In April 2011, TransMolecular's tumor-targeter was snapped up by biopharmaceutical company Morphotek, a U.S.-based subsidiary of Japanese drug giant Eisai. Though the company will not go into the details of its plans for chlorotoxin, spokesman Terry Cushmore says they intend to refine it before taking it into further clinical studies.

"We are reconfiguring the peptide to enhance its utility for diagnosis and treatment of a wide range of cancer types based on the clinical findings of the earlier studies," Cushmore says.

3. DRUG: ShK

SOURCE: Sea anemone

CONDITION: Autoimmune disease

In the warm, shallow waters of the Caribbean Sea, especially in the coral reefs around Cuba, lives a species of sea anemone called Stichodactyla helianthus. In the early 1990s, a group of Cuban researchers on a diving expedition collected some specimens to analyze their toxins. The compound they discovered has spawned an experimental drug, ShK, which is about to go into clinical trials for treating multiple sclerosis (Toxicon). It also has potential to treat a broad range of autoimmune diseases, including type 1 diabetes and rheumatoid arthritis.

Autoimmune diseases arise when the immune system mistakenly decides that one of the body's own tissues is foreign and begins to attack it. In many cases, the damage is caused by a particular group of immune cells called effector memory T-cells. These possess a unique ion channel called a Kv1.3 potassium channel without which they cannot function, and it is this channel that ShK targets.

"ShK puts the cork in the bottle," says Ray Norton at Monash University in Melbourne, Australia, who has been involved in the project since 1996. "In the presence of our compound, the cells become immobilized and wither and die."

Studies in animal models of MS have been a success, and the latest version of the compound is due to start clinical trials in humans by mid-2012.

"In MS, there's a lot of nerve damage. We can certainly stop further damage," says Norton. "Time will tell whether we can reverse damage that has already happened -- whether the innate repair mechanisms start to win out once the effector memory T-cells are taken out. We are hopeful."

Quite what such a compound is doing in sea anemones in the first place is an open question. Possibly it acts to stun the fish that they eat. Ion channel function can vary significantly from species to species, and the ion channel's role in fish could be very different from its role in our bodies.

4. DRUG: Xen2174

SOURCE: Cone snail

CONDITION: Severe pain

Divers beware: Not all pretty seashells are harmless. Pick up one containing a live cone snail and it will defend itself with its sting. The result can be fatal. Nevertheless, venom researcher Richard Lewis and his team at the University of Queensland, Brisbane, Australia, seek out these creatures along the Great Barrier Reef.

"They're a challenge to get," he says. "During the day they hide, and you can turn hundreds of pieces of dead coral over before you find a cone snail."

It's worth the hunt. Cone snails are one of the youngsters of the venom world, developing their poisonous sting just a few tens of millions of years ago. As a result, their venoms are still an evolutionary work in progress. Members of the same species can deploy very different mixtures of chemicals.

"Even individuals collected from the same place may only have a 25 percent overlap in the venoms they produce," says Lewis. That means they produce a vast array of potential medicines.

Cone snail venom is providing a complementary hunting ground to the more traditional snake venom research. Whereas snake venoms tend to target the cardiovascular system, cone snails prefer to shut down the nervous system of their prey. This means they have great potential as pain medications.

One cone snail venom compound discovered by Lewis and his team is about to go into phase II clinical trials. Code-named Xen2174, it works by boosting the signal along the body's natural painkilling nerves that run along the spine.

"In our initial safety study, we tested the drug in over 30 people with severe cancer pain, and the compound was able to produce a really quite profound reversal of pain in many of these patients, an effect that could last for many days with a single injection into the spine," says Lewis. Buoyed by their success, the researchers are also starting to develop a painkilling venom-based compound to be given orally.

5. DRUG: Cobratoxin, cobrotoxin

SOURCE: Cobra

CONDITION: Multiple sclerosis, HIV

Snake venom has a place in several ancient medical traditions. As early as the 1930s, Western pharmacists began testing cobra venom as a treatment for conditions ranging from asthma to multiple sclerosis (Expert Opinion on Biological Therapy). But in recent years, modern techniques from mass spectrometry to high-throughput lab-on-a-chip bioassays have made life easier. Chemists can pick out and identify the specific venom components with beneficial effects, eliminating some unpleasant side effects and making the whole process safer.

One such component is now showing promise for treating multiple sclerosis. Quite what triggers MS remains unknown. What is clear is that the body's immune system begins to attack the insulating sheath that protects nerve cells, causing damage that can progressively impair sensory and cognitive function and movement. Bringing the immune system back into balance has proved very difficult, but a venom peptide called cobratoxin might hold the answer.

Last year, Florida-based firm ReceptoPharm had a patent approved for a version of cobratoxin chemically modified to remove its toxicity (US patent 8,034,777). The company claims that its modified peptide halted the development of MS in 90 per cent of laboratory rats with the rodent equivalent of MS. The peptide seems to stimulate the release of a messenger molecule called interleukin-27, which puts the brakes on an overactive immune response, bringing immune activity back down toward normal levels. ReceptoPharm is planning clinical trials to assess the compound's efficacy in humans.

Meanwhile, a related venomous molecule called cobrotoxin has shown promise in treating HIV. A modified version of the toxin seems to impede the spread of the virus by blocking receptors on the surface of the body's immune cells - the same receptors that the virus would otherwise latch on to before infecting the body's immune cells.

6. DRUG: Exenatide (Byetta)

SOURCE: Gila monster

CONDITION: Type 2 diabetes

A bite from a gila monster will really mess with your metabolism. Fortunately, these lizards, found in the deserts of the southwestern U.S., are large and lumbering and most humans can easily outpace them. Nevertheless, each year a handful of people do get close enough to discover that the gila monster's bite delivers a painful cocktail of chemicals that causes nausea, fever and faintness -- and can even induce a heart attack.

However, within the venom lies a very useful compound. Called exendin 4, it triggers one of the body's insulin-releasing pathways. This effect makes it ideal for treating type 2 diabetes, a condition in which insufficient insulin is produced to keep glucose levels in check.

A synthetic version of exendin 4, called exenatide, was approved as an anti-diabetes drug by the FDA in 2005. Now the compound is being investigated for its anti-obesity properties as well, since it also slows stomach emptying, reinforcing feelings of fullness after eating.

Until around five years ago, the gila monster was thought to be one of just two venomous lizards -- the other being the closely related beaded lizard found in nearby Mexico. We now know that lizards and snakes share a common venomous ancestor, and that many lizards -- from iguanas to komodo dragons -- which were never suspected of being venomous, come equipped with venom glands (Nature).

Research into lizard venom has barely begun, so it may be a while before any other lizard-based medicine hits the pharmacy. But the wait could be worth it, says Bryan Fry at the University of Queensland, Brisbane, Australia, who has led the work on lizard toxin evolution.

"If you want to find something useful, then the more novel the venomous animal, the more novel its venom," says Fry. And that gives the best drug leads, he notes. "I think it's one of the strongest arguments we have for preserving biodiversity."

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