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June 02, 2012

Is Sugar Carcinogenic?

How is sugar used in the cell ?
Every cell in our body needs energy in order to survive and perform its functions. Our biochemistry has evolved over billions of years to extract energy from simple sugars, like glucose and fructose. I mentioned the evolutionary ancient-ness (is this a word?) for a reason. In the beginning (relax, I am not getting into the creation debate) the atmosphere was poor in oxygen. Yet cells had to extract energy from their nutrients. The solution? Extract energy from glucose without the participation of oxygen. This process is called anaerobic glycolysis, and even today, there are anaerobic bacteria that survive solely through glycolysis. This process nets a measly 2 ATP molecules (these are the molecules that store the energy necessary to drive chemical reactions in the cell), and two 3-carbon molecules of pyruvic acid.
As the ancient atmosphere became enriched with oxygen it became possible to oxidize pyruvic acid, the end product of glycolysis, and extract another 30-36 ATP molecules. At about the same time, a species of parasitic bacteria invaded the primordial cells.  The two finally settled into a cozy partnership: the cell will provide nutrients and a secure environment to the bacteria, and the bacteria will provide their capacity to break down pyruvic acid through a chemical process called oxidative phosphorylation using a series of enzymes that make up the electron transport chain, providing the cell with the additional 30 ATP per glucose molecule. And so were born our mitochondria, the tiny powerhouses that inhabit all our cells (except red blood cells).
What does all that have to do with cancer?
Now that we know why the cell needs glucose, and how it obtains the energy it needs out of glucose molecules, we can rationally examine the scary prospect that too much glucose can facilitate cancer.
Cancer cells, like any healthy cells, require glucose as their energy source. But, if you measured the amount of lactic acid in a solid tumor you would find a high concentration, and if you measured the pH -it would be lower than in normal tissue. The reason is that cancer cells depend to a large extent on anaerobic glycolysis. And we know that the end-product of that is pyruvic acid, which makes the tumor tissue acidic; hence the low pH. What about lactic acid? It is the product of pyruvic acid when oxidation is not possible. Of course we know it from first-hand experience: when you exercise a muscle to the point that the oxygen supply cannot keep up, you create a lot of lactic acid, which is a pain in the…muscle.
But, you are wondering, a tumor doesn’t exercise, so why the anaerobic conditions? Enter the evil genius of tumors. When a solitary cell accumulates the proper mutations it becomes a tumor cell, a process called carcinogenesis. The cell divides into daughter cells, those divde again, and so on -until there is a tiny tumor, made of millions of cells. In a sense, a new tissue was created. Except that normal tissue has its own extensive blood supply, but not this tiny tumor: it is made up solely by the tumor cells.
So how is a tumor to get its oxygen and nutrients?
The way the tumor cell copes with this dilemma is two-fold. First, it derives it energy from whatever little glucose is available using anaerobic glycloysis and getting 2 ATP molecules per glucose. This state of affairs cannot last forever, because the cell would require enormous amounts of glucose to get enough ATP to fuel its metabolic functions. So the second pillar of the strategy employed by the tumor is to secrete chemicals that stimulate blood vessels in the surrounding normal tissue to sprout new branches that penetrate the tumor and supply it with nutrient and oxygen. This process, called angiogenesis (literally formation of blood vessels) allows the tumor to undergo a new growth spurt, and metastasize to distant organs.
As I said, the initial tumor depends heavily on glycolysis, and because of its inefficiency in extracting energy out of glucose it has a voracious appetite for the sugar. And from that, the “logical” conclusion that sugar is carcinogenic.
Except that it isn’t. Glucose does not cause cancer, or else all living organisms would seccumb to cancer and die. Glucose indeed is utilized by  cancer cells to a much larger extent than normal tissue cells. But they get this extra glucose by extracting it a lot more efficiently.  They have glucose transporter molecules on their surface that grab the molecules out of the tissue environment before the normal cells can get to them. So what would one accomplish by depriving himself of glucose? One kills his normal cells before the tumor cells feel the pinch.
Of course, this is a bit oversimplified, but the general idea that glucose does not cause cancer, and deprivation of glucose will not kill the cancer, is valid.
What about the other detrimental effects?
I am in complete agreement that glucose can be harmful. It is associated with obesity, metabolic syndrome and type 2 diabetes. It has been shown to damage blood vessels. it is even bad for your teeth. So why eat it at all? You can get all the glucose you need from complex carbohydrates, a much healthier metabolic form.
So try to limit your glucose intake to no more than 15 grams a day (the amount in one can of soda). Get the rest of your energy requirements from grains, fruits and vegetable. And don’t worry about the cancer hype.
by
AKSHAYA SRIKANTH
Pharm.D Resident
Hyderabad, INDIA

May 31, 2012

POST MARKETING SURVEILLANCE IN INDIA


Regular monitoring of clinical data of both old and newly approved drugs is considered necessary to ensure  their safety and efficacy as three phase clinical trials  cover only a few thousands of subjects. Adverse drug reactions of some of the new drugs will be only known when they are launched in the market and lakhs of people start using them. Post marketing surveillance and regular monitoring ADRs of drugs is, therefore, critical for the health authorities to decide their safety. Known also as phase IV study, the post marketing surveillance is considered helpful for  the pharmaceutical companies to improve the potential of the marketed product. This phase helps the pharma companies in finding data for newer indications and new markets for which the drug product had not been initially approved by the drug authorities. The need to have regular post marketing surveillance was found extremely important in the wake of recall of quite a few drugs from the market in recent years. Some of the high profile drugs like rosiglitazone, nimesulide, cisapride and phenylpropanolamine were withdrawn from the world markets after years of granting marketing approvals. That would mean that millions of patients had taken those unsafe drugs for years without knowing the harm these drugs might have been caused to them.
In India the decision to recall unsafe drugs from the market is taken usually after the US or European regulatory authorities take such a step. This is mainly because of the fact that post marketing studies are not undertaken by most of the pharmaceutical companies in India. Although submission of post  marketing surveillance data is mandatory on the pharmaceutical companies , most of the companies do not care to submit such reports to the DCGI. The Parliamentary standing committee on health & family welfare has taken serious note of this deficiency in enforcement of this rule by the office of the DCGI. In its investigation, the committee found that in the case of most of the approved drugs, the pharmaceutical companies were not submitting Periodic Safety Update Reports (PSURs) listing side effects, fatalities, injuries etc. These reports are expected to be submitted once every six months in the first two years and then annually in the following two years. The Committee asked the health ministry to direct CDSCO to send out a warning to all manufacturers of new drugs to comply with mandatory rules on PSURs or face suspension of marketing approval. Pharmacovigilance or ADR monitoring of the drugs by CDSCO has also been rather weak for several years and it has come into existence only from 2010. Even after launching of the pharmacovigilance programme two years ago, it has not made  much progress as yet . In the first phase of the programme, the target was to set up 40 ADR centres, but just 22 were set up. Although 60 more centres were planned last year at an investment of Rs.60 crore, only 40 more added subsequently. In an atmosphere of poor compliance in submission of PSURs by pharmaceutical companies, strengthening of the network of pharmacovigilance centres is the only option left to the government to track the drug safety in the country.
Source: PB
by
AKSHAYA SRIKANTH
Pharm.D Resident
Hyderabad, India

May 29, 2012

ENDOCARDITIS

Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves.Endocarditis is characterized by a prototypic lesion, the vegetation, which is a mass of platelets, fibrin, microcolonies of microorganisms, and scant inflammatory cells.There are multiple ways to classify endocarditis. The simplest classification is based on etiology: either infective or non-infective, depending on whether a microorganism is the source of the inflammation or not. 
People with poor dental hygiene, heart valve abnormalities, congenital heart disease, and weakened immune systems are at higher risk for endocarditis.
Endocarditis can cause direct damage to the heart, or damage to other organs from bacterial emboli, or pieces of bacteria that “break free” from the heart.
Endocarditis is diagnosed by blood tests and ultrasound pictures of the heart.
Most cases of endocarditis can be treated with intravenous antibiotics, although a few serious cases require open-heart surgery.
The best method of preventing endocarditis is maintaining good oral and general health.  People with heart valve abnormalities, congenital heart disease, or who have had endocarditis previously may benefit from preventive antibiotics prior to dental or surgical procedures. 
RISK FACTORS FOR ENDOCARDITIS
Because endocarditis is usually caused by bacteria entering the bloodstream and accumulating on the valves of the heart, people at risk for the condition include those with a tendency for bloodstream infection and those with abnormalities of their heart that allow for accumulation of the bacteria.
Conditions increasing the risk of bloodstream infection:
  • Poor dental hygiene
  • Intravenous drug use
  • Surgeries or procedures, especially those involving the mouth or the gastrointestinal system
  • Medical conditions that can weaken the immune system (e.g. diabetes, severe kidney disease, HIV/AIDS, cancer)
  • Elderly age
  • Prolonged use of intravenous catheters (e.g. in hospitalized patients, patients receiving home intravenous therapy, or patients receiving hemodialysis for kidney failure)
  • People recently hospitalized
Conditions increasing the risk of accumulation of bacteria in the heart:
  1. Abnormalities of one or more of the heart valves (e.g. malformed valves, leaky valves, rheumatic heart disease)
  2. Congenital heart abnormalities (e.g. “holes” in the heart)
    1. Artificial heart devices (e.g. mechanical heart valves, pacemakers, defibrillators)

COMPLICATIONS OF ENDOCARDITIS
Endocarditis can cause two types of complications:  complications to the heart from direct damage by the bacteria, and/or complications to other organs from bacterial emboli, or pieces of bacteria that break free from the heart.
  • Valve damage – When the bacteria gather on the valve leaflets, they can prevent proper opening and closing of the valve.  Even after the bacteria have been treated with antibiotics, the damage to the valve can be permanent.  If the damage is sufficiently severe, it may require surgical replacement of the valve.  In addition, the damaged valve is at higher risk for developing endocarditis in the future.
  • Congestive heart failure – If the bacterial accumulation is sufficiently large, the valve can fail and result in weakening of the pumping action of the heart, a condition known as congestive heart failure.  This is a serious complication, and usually requires immediate surgery to replace the valve.
  • Slow heart beats – If the bacterial infection affects the “wiring” of the heart, then the heart may skip beats or beat very slowly.  If this condition results in dizziness or passing out, then a pacemaker may be needed.
Complications from bacterial emboli:
In approximately 11%-25% of patients with endocarditis, small pieces of bacteria, or emboli, break off from the main area of infection in the heart and travel through the bloodstream. As they travel, they may lodge in a blood vessel, block it, and damage the organ that the blood vessel supplies.  Common organs that are affected include:
  • Brain – Bacterial emboli can travel from the heart to the brain and cause a stroke.
  • Kidney – Bacterial emboli can travel from the heart to the kidney and cause kidney damage or failure.
  • Musculoskeletal system – Bacterial emboli can cause inflammation of the muscles and joints.
  • Other organs – Emboli can affect the eyes, spleen, liver, lungs, or intestines.
Symptoms of endocarditis usually begin within 2 weeks after infection of the blood.
Common symptoms include:
  • Fever
  • Chills
  • Fatigue
  • Excessive sweating, especially at night
  • Loss of appetite
  • Unexplained weight loss
  • Back or joint pain Blood in the urine
  • New rashes (especially red, painless skin spots on the palms and soles) Red, painful nodes on the pads of the fingers and toes
  • Shortness of breath with activity
  • Fluid buildup in arms or legs (swelling of feet, legs, or abdomen)
  • Sudden weakness in the face or extremities suggestive of a stroke  
TREATMENT
Treatment of endocarditis requires antibiotic therapy and, in rare and serious cases, open-heart surgery.
Antibiotics - If endocarditis is detected early and the bacterial accumulation (known as a “vegetation”) covers only a small area (less than 10 mm), intravenous antibiotic therapy for 2 to 6 weeks is often the only treatment necessary. Once antibiotic therapy is started, most patients quickly improve, with less fatigue, improved appetite, and a disappearance of fevers and chills. However, this does NOT mean the infection is gone. Treatment should be continued as prescribed because it usually takes the full 2 to 6 week course of antibiotics to kill the last of the infecting organisms.  Stopping this treatment early can cause the infection to re-occur.
Open-heart surgery – Higher risk infections, such as vegetations larger than 20 mm or infections causing congestive heart failure, may require open-heart surgery to remove infected tissue, correct pre-existing heart disease, or repair the heart valve damage. Typical indications for surgery are heart failure due to damaged valves, uncontrolled infection into the heart (abscess formation), recurrent emboli, and relapse after appropriate medical therapy.
by
AKSHAYA SRIKANTH
Pharm.D Intern
INDIA

May 28, 2012

Pharma Social Networking Benefits


Facebook, Twitter and more have led us to social media mayhem! Pharma companies are no exception, with many companies having a web presence through social media. Great pharmaceutical centers use social media platforms to release press updates, offer exclusive deals and keep connected with their clientele. Pharmaceutical social media is on the rise, and we have outlined seven ways in which pharma companies use social media most effectively to build their businesses. They are as follows:  
  1. Pharmaceutical companies add social bookmark links to their most important webpages to increase the rate of sharing. With a single embedded line of script, hundreds of viewers can express their “like” or “comments” on content regarding new drugs and news about the direction of the pharma company. For instance on one major pharma company's website found you can find Recommend this page buttons for Facebook, Twitter, Email and more.
  2. Pharmaceutical companies build blogs and teach people about common pharmaceutical practices and uses. By having a reliable foundation of content, pharmaceutical companies do a huge favor for the inquisitive public. When people identify a further need for a pharmaceutical company’s services after their search, the pharmaceutical company then sees the fruits of its labor regarding informational blogs and posts. See how this works at this pharma company blog.
  3. For every video project purchased and recorded for pharmaceutical companies, webmasters of these drug giants should ensure that there’s an embeddable web version of the video for improved sharing across sites. What’s better than having one video up on YouTube? Having that video being linked on blogs across the country so every time the video is played remotely, an expanding audience hears the pharmaceutical company’s mission.
  4. Pharma companies are extremely good at tagging and using other metadata to enhance the public’s ability to find the information they provide. Simply titling a video and creating a brief description isn’t enough – tagging your content makes it more relevant for anyone searching for tag-related content.
  5. By regularly Tweeting out updates, pharma jokes, questions for clientele and more, pharma companies reveal their underlying personalities. A quick look at how this is being done on Twitter shows how career openings can be blasted to several thousand people every day via Twitter!
  6. Pharmaceutical companies establish platforms that communities flock to – groups for charitable races, large sponsored events and more are made possible through organization via social media. Check out how pharma companies are increasing support to some of their favorite charities (note the "share this" button!) in this article.
  7. Pharmaceutical companies assist other companies in starting up within social networks which strengthens their business ties within the social media site. By developing web-based B2B connections, drug manufacturers can strengthen bonds with packaging companies, shipping companies and other complimentary industries with which they do business.
Technology progressively gets better facilitating communication between organizations and individuals. Public opinion is highly coveted and with social media we no longer need to rely on polsters to get this information. Because of this the internet has assisted in directing pharma companies' research, development and marketing efforts.
by
Akshaya Srikanth
Pharm.D Resident 
India

NARCOANALYSIS: Source of Finding the Truth

                                            Narcoanalysis is a controlled administration of intravenous hypnotic medications called truth drugs (barbiturates or other drugs like suxametanium/thiopentone/sodimamytal/scopolamine called truth drugs/serum), which induce a sleeplike state in the person. Under the influence of the drug, the accused has garbled speech and tends to talk about fantasies, and labors under delusions. Their state resembles that of a person in delirium, so these tests cannot be treated accurate. This technique is often used by investigating agencies in criminal cases, as an interrogation technique. The scientific validity of the test has been questioned by medical professionals, ethics forum and the legal validity has also been debated in several international and national cases.
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The truth serum or sodium pentothal is the same substance that in larger dosages is used to induce a deep coma–like state for executions by lethal injection in USA. A large dose of the drug is lethal; a test could result in coma or even death. It can be difficult to determine the correct dose of the drug.
In the United States of America, the New Jersey Supreme Court banned the use of narcoanalysis in Pitts. V. State for lack of scientific reliability. In India as well, the use of narcoanalysis has been questioned in courts.
The main argument against Narcoanalysis is that it is infringement of the fundamental right under Article 20(3) of the Constitution, which provides for a privilege against self-incrimination. It can also be construed as violating human rights of privacy, and the right to health. At the same time, narcoanalysis is an invaluable tool for investigators. Since the results of the test cannot solely be used to prove the guilt of the accused, advocates of narcoanalysis point out that it is not violative of the right against self–incrimination. Statements made under the test have to be corroborated by further evidence.
Source: Medico-legal Updates
by
Akshaya Srikanth
Pharm.D Internee
Hyderabad, India