FORENSIC OHTS, RIPS ISLAMABAD

BIOPHARMACEUTICS PAST PAPERS

Upon Request from students of RIPS ISLAMABAD

FDA Warns of Rare Acetaminophen Risk

Acetaminophen, a fever and pain reliever that is one of the most widely used medicines in the U.S., can cause rare but serious skin reactions, warns the Food and Drug Administration (FDA).

Although rare, possible reactions to acetaminophen include three serious skin diseases whose symptoms can include rash, blisters and, in the worst case, widespread damage to the surface of skin. If you are taking acetaminophen and develop a rash or other skin reaction, stop taking the product immediately and seek medical attention right away.

ANTI SENSE DRUGS

ANTI SENSE DRUGS

Antisense drugs are drugs that seek to block DNA transcription or RNA translation in order to moderate many disease processes. Antisense drugs consist of nucleotides linked together in short DNA or RNA sequences known as oligonucleotides.

Oligonucleotides are designed knowing the target DNA/RNA to bind to specific DNA or RNA sequences or regions (eg, messenger RNA) to block transcription or translation of that targeted protein. An oligonucleotide that binds complementary (“sense”) mRNA sequences and blocks translation is referred to as antisense.

To further stabilize the drug, many chemical modifications have been made to the oligonucleotide structure. The most common modification used involves substitution of a nonbridging oxygen in the phosphate backbone with sulfur, resulting in a phosphorothioate-derived antisense oligonucleotide. Some of these drugs have been designed to target viral disease and cancer cells in the body.

Antisense drug discovery and research & development.

For this approach to be useful, the etiology and genetics of the disease must be known. For example, in the case of viral infection, known sequences belonging to vital genes can be targeted and inhibited by antisense drugs. Many antisense sequences are usually tested to find the best candidate, since intra- and intermolecular interactions can affect oligonucleotide activity and delivery. Though oligonucleotides are relatively well internalized compared to rDNA molecules, cellular uptake is often low enough to require delivery systems, such as liposomes. Antisense and gene therapy approaches have also been combined using viral vectors to deliver an antisense sequence. In this case, the transgene is transcribed into an mRNA molecule that is antisense and therefore binds to the target mRNA. The resulting RNA:RNA interaction is high affinity and results in inhibition of translation of that mRNA molecule.

History of antisense drugs

In the early 1970s, Paul Zamecnik (pronounced ZAM-es-nick) was studying a cancer-causing chicken virus that transmits its genetic information via RNA, a chemical cousin of DNA. Zamecnik and his colleagues at Massachusetts General Hospital found that, as the virus replicated, its RNA looped around on itself. They speculated that if they could block this step, they could stop the bug in its tracks. So they constructed a short piece of DNA designed to stick to the virus’s single strand of RNA and thereby gum up its works. The RNA encoded the virus’s proteins; functionally, it made sense, so the researchers called it the “sense” strand. The DNA molecule (called an oligo-nucleotide) was its chemical opposite-the “antisense.” Zamecnik mixed the designer DNA snippet with infected chicken cells, and voil-no cancer. He and colleague Mary L. Stephenson suggested that antisense molecules could be used to treat all sorts of infections-as well as cancer-by preventing RNA from being translated into the proteins the invaders need to live.

 When the work appeared in the January 1978 Proceedings of the National Academy of Sciences, no one believed the experiment had worked. “It had been…a dogma that oligonucleotides didn’t get into cells,” Zamecnik says. The work languished in obscurity until the mid-1980s, when technological advances made the experiments easier to repeat. As biochemists began to see anti-sense as a magic bullet, companies sprang up to capitalize on the “new” technology. It wasn’t smooth sailing-difficulties with stability and specificity to targeted RNAs hindered its adoption. But now the technique seems ready to pay off.

On 24 August 1998, the US Food and Drug Administration (FDA) approved the world’s first antisense drug, fomivirsen, developed by Isis Pharmaceuticals Inc.  , a small biotechnology company based in Calsbad, California. The FDA approved the drug for the treatment of CMV retinitis, a viral infection that causes blindness in AIDS patients. Following Isis’ success, there is now increasing interest in antisense technology. Isis is currently conducting ongoing clinical trials of other antisense drugs for the treatment of common medical conditions, including rheumatoid arthritis, cancers and Crohn’s disease, a serious intestinal illness.

More than 20 other antisense drugs, most targeting cancer and viral infections, are in clinical trials. And Zamecnik (the founder of Isis), now nearly 90 years old, is still researching antisense treatments for drug-resistant forms of tuberculosis and malaria.

Diet affects sleep - Study

A new study from the University of Pennsylvania's Perelman School of Medicine shows an association between what one eats’ and how one sleeps,reported BBC health. "In general, seven to eight hours of sleep each night is most likely an experience of overall better health and well being.

Question that was asked in the study, `Are there differences in the diet of those who report shorter sleep, longer sleep, or standard sleep patterns?'" said study researcher Michael A. Grandner, Ph.D., of the Center for Sleep and Circadian Neurobiology at the university.

Researchers examined the daily calories and foods consumed - down to a glass of water. They also gathered information on the amount of time the study participants slept, putting them into four categories: "very short" sleepers, who slept fewer than five hours a night;"short" sleepers, who slept five to six hours a night; "standard" sleepers, who slept seven to eight hours a night; and "long" sleepers, who slept nine or more hours a night.

And researchers did find an association between the number of calories consumed and how long the study participants slept. Those who consumed the most were more likely to be "short" sleepers.

Interestingly, "normal" sleepers were the next type to consume a lot of calories, followed by "very short" sleepers and then "long" sleepers, researchers found.

The researchers also identified different associations between sleep time and the types of nutrients the participants ate.

Overall, researchers noted that the very short, short and long sleepers consumed a less varietal diet than those who were considered normal sleepers.

The question is now whether changing eating habits can actually affect sleep, as the study only showed an association.

KFC USES NO CHICKEN --- JUST A RUMOR OR A FACT?

KFC USES NO CHICKEN --- JUST A RUMOR OR A FACT?...................... Whats your opinion?


KFC has been a part of American traditions for many years. Many people, day in and day out, eat at KFC religiously. Do they really know what they are eating? During a recent study of KFC done at the University of New Hampshire, they found some very upsetting facts. First of all, has anybody noticed that just recently, the company has changed their name?

Kentucky Fried Chicken has become KFC. Does anybody know why? We thought the real reason was because of the "FRIED" food issue.
IT'S NOT!!

The reason why they call it KFC is because they can not use the word chicken anymore. Why? KFC does not use real chickens. They actually use genetically manipulated organisms. These so called "chickens" are kept alive by tubes inserted into their bodies to pump blood and nutrients throughout their structure. They have no beaks, no feathers, and no feet. Their bone structure is dramatically shrunk to get more meat out of them. This is great for KFC.

Because they do not have to pay so much for their production costs. There is no more plucking of the feathers or the removal of the beaks and feet. The government has told them to change all of their menus so they do not say chicken anywhere. If you look closely you will notice this.

A new type of malaria vaccine could beat all strains

JENNIFER REIMAN, GRIFFITH UNIVERSITY

A new type of malaria vaccine that has been shown to be safe in mice is about to start trials in humans.

This promising vaccine is different to other approaches to stopping the deadly disease because we use the whole malaria parasite in it. And it is able to protect against multiple strains of the illness.

Malaria and the need for a vaccine

Malaria is a mosquito-borne disease infecting nearly 250 million people each year across 109 countries. It causes approximately one million deaths each year, mostly among African children under the age of five.

The parasite has a complex life cycle with half of it lived within the female mosquito, and the other half in the human host (first within the liver and then by infecting red blood cells).

When the parasite bursts out of infected red blood cells, it destroys the cells and causes the symptoms of malaria.

Current preventive measures against malaria include those that act on the mosquito including insecticide-treated bed nets (physical barrier) and indoor residual spraying of chemicals (insecticides) to kill mosquitoes when they land on the walls.

If you’re infected, anti-malaria drugs (artemisinin-based combination therapies) are used to kill the parasite, but not everyone has access to them.

What’s more, mosquitoes and malaria parasites are continually developing resistance to current chemicals and drugs, frustrating efforts to protect against the illness.

There is no licensed vaccine against malaria, and the most advanced experimental one in clinical trials, RTS,S is showing little protection.

Our vaccine

Researchers around the world have been working on a vaccine for malaria for over 80 years. The team I’m in has been working on the problem for over 20 years.

Based on previous results from our group showing that a vaccine containing low doses of the dead parasite protected against malaria, we decided to use the whole parasite while it is still inside the red blood cell (the second stage of malaria infection) in our vaccine.

Colleagues in North America had previously showed that treating sporozoites (the malaria parasite at the stage when it is transmitted from an infected mosquito) with a particular drug protected against infection with sporozoites of all strains.

We used this same drug to treat infected red blood cells. The drug binds to the parasite’s DNA and prevents it from multiplying.

We treated red blood cells from mice infected with malaria with the drug in a test tube, then washed away the excess drug and gave the remaining treated cells to mice. This is our vaccine.

Later, we infected the mice with malaria to see if they were protected. We found that mice given our vaccine before infection did not develop as many parasites in their blood. Some of the mice had so few parasites that we were unable to see them when we looked at the blood under a microscope.

And even though mice were immunised with only one strain of malaria and infected with a different strain, they were also protected by our vaccine. That means that our vaccine protects against all strains of malaria.

How our vaccine is different

Previous vaccines have been able to activate humoral immunity (protection mediated by antibodies). These vaccines stimulate to body to make antibodies that bind to proteins on the surface of the parasite and can prevent parasites from invading new red blood cells. Or they can make antibodies that bind to the surface of infected red blood cells and are important in their removal.

These vaccines have, for the most part, not been successful. Malaria can hide from these antibodies by making a new version of the protein that won’t be recognised by the antibodies.

People who live in malaria infected areas do eventually develop protection against malaria symptoms. But this protection doesn’t occur until they have been infected with multiple strains of malaria (and only if they don’t die from one of the infections first).

Unlike naturally acquired immunity to malaria, our vaccine works by turning on cell-mediated immunity which involves T lymphocytes (a type of white blood cell). These T lymphocytes are able to recognise all kinds of proteins including those hidden inside the malaria parasite.

The hidden proteins may be shared between the various strains of malaria and we suspect that’s why our vaccine protects not only against the strain given in the vaccine but all strains of malaria.

The next steps

The results from our studies in mice has prompted us to test our malaria vaccine in humans. Within the next few months, we will begin a human clinical trial testing the vaccine made in human red blood cells that are infected with the human malaria parasite.

If results of the study in healthy Australian volunteers is promising, the vaccine will progress onto studies in areas where malaria is present. We are very encouraged by the results so far and optimistic that our vaccine approach will aid the fight against this debilitating illness that affects so many people around the world.