Sunday, September 9, 2007

UPDATE!!!

So I am back after a lull of almost 4 days.

We are soon coming out with a website which is yet to be named but the countdown has certainly begun ,which is the reason for this lull. But anyhow I have come out with the "Drug of the Week" post below.
I start off with the alphabet "A" for condition Alzheimers and the drug "Axura"

I have got a post below the Drug of the week which has been sent by a visitor, I would be really glad if you could please comment on that post.

There is more to come this week, so keep visiting the blog and continue your lovely support!!!!
Thanks.

Drug of the Week: Axura

So here is the Drug of the Week: Axura


Every tablet of Axura contains "MEMANTINE". This tablet is used in treatment of Alzheimers.The treatment regime of Alzheimers is complex, just like the disorder. While most of the drugs used in the tratment of Alzheimers fall in the class of Cholinester Inhibitors, which prevent the formation of Acetycholine, Memantine acts a bit differently.



Memantine is an NMDA receptor antagonist, it prevents continous stimulation of NMDA receptors by Glutamate.



But how does this dug improve conditions of Alzheimers patient is really interesting to learn!!!!




In normal conditions Glutamate activates NMDA receptors . In order to prevent excessive influx of calcium ions , Mg ion(magnesium) blocks the ion channel under resting conditions. If the NMDA receptor is activated by Glutamate, and simultaneously post synaptic neuron is depolarized Mg ion leaves the ion channel, and calcium flows in which is makes learning possible. Therefor ein Normal condition learning is based on sufficient signal over base line activity i.e enough calcium influx for sufficient signal to noise ratio.




Now in the picture it is observed that there isa good signal to noise ratio important for learning.



However in physiological conditions like Alzheimers NMDA receptors are activated by glutamate more or less continously. Under such conditions there is increased calcium influx which enhances noise and so probability of detecting signal decreases. This progresses to cognitive defects.
In this picture it is seen that the signal to noise ratio is not clear making learning difficult especially in patients suffering with Alzheimers






The reason for excessive Glutamate presence and continous activation of NMDA receptors is because excess beta amyloid prevents recycling of Glutamate i.e uptake of Glutamate by Glial cells and therefore excess glutamate masks signal transmission which results in continuated activity of NMDA receptors.



However Mg is an endogenous NMDA antagonist but has a strong voltage dependency and low affinity which results in fast blocking kinetics ,other NMDA antagonists like Dizocilpine have high affinity but are associated with slow kinetics and very weak voltage dependency.This molecule is a find beween both Mg and Dizocilpine.



Due to less voltage dependency mementine is effective than Mg , however after synaptic activations mementine like Mg can leave NMDA receptors due to voltage dependency and fast unblocking sites. It suppresses synaptic noise but allows physiological synaptic signal to be detected. This provides symptomatic neuroprotection and restoration of synaptic plasticity.

This picture shows how Mementine by blocking the NMDA receptors exerts its neuroprotection activities and when there is a physiological synapse, how it unblocks the receptors and improves cognitive activities.


The best part of this post is right here!!!

Incase you have not understood the whole text with simultaneous diagrams then the mode of action of Memantine can be seen in an animated form. Just click on the URL below and clear your doubts. http://www.memantine.com/en/mode_of_action/animation/

Saturday, September 8, 2007

ANTIBIOTIC BROTHERS IN HARMONY TAKE AVENGE

An interesting post sent by one of the visitors!!!
Textbooks have taught us that antibiotics that are Bactericidal fall into 3 different classes: One that inhibit DNA replication and Repair,One that inhibit protein synthesis and the other which prevent cell wall synthesis. Research on different antibiotics from Dr. Collins Lab at Boston University has bought an extension to this textbook fact.
Though these three types of antibiotics have different affects on bacterial cells, they all converge on a pathway that causes avenge by generating Oxygen Free Radicals.
Earlier this year Professor Collins group reported that one class of antibiotics did produce hydroxy free radicals and caused DNA and protein damage in bacterial cells. To test this his colleagues Michael Kohanski and Daniel Dwyer from Boston University exposed E.Coli and Staphylococcus Aureus to each one of the three classes of antibiotics. Using Floroscent Dyes they looked for the presence of hydroxy radicals in both these bacterial cells.
In another experiment to show that hydroxy radicals was responsible for cell death,they blocked the radical formation by giving antioxidants and this resulted in the survival of bacteria with all types of Antibiotics.
However the other class of antibiotics, i.e the Bacteristatic class didnot inhibit bacterial growth by increasing free radicals in the bacterial cell.
It was also observed that both the Tri Carboxylic Acid cycle(TCA cycle) and electron transport chain of bacterial metabolism were responsible for the production of free radicals in the bacterial cell and so these antibiotics used the same pathway to increase the free radical formation.
The researchers hope that this study would help in designing of newer antibiotics which can be powerful at very low dosages.

Just staying with this topic of Antibiotic Prescription to the patients,I just wanted to know when so much hype has been going around PERSONALIZED MEDICINE, do doctors ever think while prescribing medicines what effect would antibiotic have on a specific patient!!!
Or is it just that they feel confident that there would be really no adverse affects based on their obseravtion from years treating a specific population.
Please comment.

Tuesday, September 4, 2007

80 year old Schwazeneggar's in the future?


Dr. See-Jins Lab at John Hopkins University School of Medicine has been sucessful in creating a "mighty mutant mice". His lab has come out with a "genetic recipe" of creating a mice which will have 4 times muscle mass than the normal mice.BRAVO!!!
This is clearly evident from the picture on the left. A normal mice and a strong, mutant, muscular mice is seen in every photo.

These mice differ from the normal mice by having almost 73% excess muscle build. The genetic recipe consists of suppressing one protein and overexpressing the other.

These "super-sized, heavy build" mice cannot produce a protein called Myostatin and can produce too much of Follistatin. It is this combined genetic supressiona nd overexpression that has resulted in these mutant mice.

Though the possible molecular mechanism is yet to be elucidated, Dr. See-Jin suggests that Myostatin might restrict muscle development and Follistatin prevents Myostatin from action ,works well in the absence of Myostatin. So he feels there might be more that one mechanism of follistatins action.

Another point to be noted here is that Myostatin is virtually undetectable in Humans and so more targets of Follistatins need to be identified in Humans.But once these targets are identified, then new drugs for muscle development could be produced and this would be hardly resisted by any of the present generation Athletes.

So with this discovery will we have 80 year old Schwazeneggars? The answer from the discoverer was "No".

He says that if new drugs would be discovered then these would prevent muscle weakness in elderly people as well could treat various symptoms of AIDS, Duchennes,Muscle Wasting etc.

However this discovery could pave way for more muscular animals like cattle or sheep to have more muscular and tastier meat.

However there is still a long way to go. But just imagine what would happen if this kind of drug would be available Over the Counter to the public !!!!

Please do send me your comments.


Monday, September 3, 2007

I am Sorry!!!

I am sorry so as to not update this blog from last 2 days, I was just waiting for more people to come and visit this Blog. I hope you understand.
I apologise to all the viewers again.
But I am back with another post below and just waiting for your comment on this interesting topic.

Pheromones in Animals accepted, but Pheromones in Humans??

This is really Interesting!!!
Recent research at Howard Hughes Meidcal Institute has shown that Trpc2, an Ion channel expressed in Vomensoral Neurons in mice is responsible Sex-Determination.
Male mice that are deficient in this ion channel Trpc2 had impairement in sex-determination and male-male aggression. The focus of this study was on female mice. Mutant Trpc2 mice showed a reduction in female specific behaviour like lactation and maternal aggression.The most interesting feature observed was these mutant females showed unique characteristics of male sexual courtship behaviours like pelvic thrusts.The same behavorial phenotype was observed when Vomensoral Organs were surgically removed but the oestrous cycles and sex-hormones levels were not disrupted.
This showed that VNO(Vomensoral Organ) mediated pheromones input in Wild Type females represses male behaviour and increases female specific behaviour.
This study also proved another point and that there were functional neuronal circuits for male specific behaviours in normal female mouse brain.

This gets me to a very interesting question that has always been a controversy
Wether Human Olfactory Signals exist or not??
Though much has been talked and written about, has any Human Pheromone been isolated and has it's activity been demonstrated or not is the biggest question I have.Can I get an explanation for this.
Looking for your comments

Saturday, September 1, 2007

OK!!! I Have an Idea.

Hello Everyone.

Now I am on a spree to make my blog most readable and Interesting.

For the "Starters", I have thought of 3 interesting things.

1. Starting off next week I will have a new section called the "Drugs of the Week". In this we will have something written about a Drug treating any condition. Something that must be there is the name of the Drug/Molecule , the disease it treats and ofcourse its molecular targets and mode of action.Many more things can be written "if possible". The interesting thing here is that you as a reader will get an opportunity to post your drug of the week. You can send me your "Drug of the Week" to the following email address: dharani.burra@gmail.com . The best and the most interesting one will be selected and posted on this blog with the senders name. If you have observed in the first statement I have mentioned "Drugs of the Week". The other drug post would be made by me ( I donot want to leave this post empty if I donot get any response from you, I hope you all understand!!!). Your "Drug of the Week" should reach me by Thursday's of every week and the "Drugs of the Week" would be updated every Saturday.

2. The second interesting thing I have thought of is "BioTechnique of the Week". This post "for the start" would be posted by me and later you all preciuos readers will be given a chance. "Please donot loose Heart".

3. The third thing I am introducing is the"Interesting Post of the Week". You have a chance to vote. You can send me your entries to the following email address:dharani.burra@gmail.com by Friday evening.

THAT IS ALL I HAVE THOUGHT OF.IF YOU HAVE ANYMORE SUGGESTIONS TO MAKE THIS BLOG INTERESTING, PLEASE DO LEAVE A COMMENT. "AAPKA HUKUM SAR ANKHON PAR"
Thanks

Interesting Cancer "Vaccine" soon!!!

Yes it is true.
This cancer "vaccine" is not unique because it targets Telomerase(An enzyme that maintains the length of telomeres in Cancer cells so that they divide continously) but it is unique because of the way it targets this enzyme.
This "vaccine" which works on basic Immunology Principles is being designed by Duke University Medical Centre and Geron has completed its phase 1 and 2 clinical trial on prostrate cancer patients. This is an ex vivo process where the patients dendritic cells(which act as Antigen Presenting cells) are isolated from the blood and pulsed with RNA of the Telomerase protein component (hTERT) and then injected back into the patients body which then instruct T cytotoxic cells to kill tumor cells that expressed telomerase.
I feel this is a very innovative cancer treatment.For more details go to the website: http://geron.com/

Now my question is wether this can be called a VACCINE.
From what I know a Vaccine is given in order to prevent a condition, not when a patient is already having that specific condition. But then if I am wrong then this will be the worlds first Vaccine which is killing Tumors rather than preventing them.
Tell me what do you think?
Waiting for your comments.

I have another question, but that will be after I find the answer for this one.

PATIENCE IS THE KEY


Here is the timeline of Glivec:

As usual patience is the key here. If you see the timeline, you can observe the amount of time, money, hardwork that has gone into the making of this drug. 46 years is not a joke!!!

So according to me PATIENCE,PATIENCE AND PATIENCE IS THE KEY TO SUCESS FOR ALL THE ASPIRING FUTURE DRUG DEVELOPERS INCLUDING ME OFCOURSE!!!!

All the fuss about "Bechara" Glivec!!!

It happens only in India. Isnt it?

The fuss about Glivec is a hot topic at my-biopedia.

There was a petition given by the Association of Cancer Patients in India against the rights given by the Indian patent office to Novartis to have exclusive sales right of their drug Glivec(Imanitib) in India.

The reason for this petition was that Glivec's exclusive sales right to Novartis would disallow the sale of all the other cheaper generic drugs that are already existing. As a matter of fact a months dosage of Glivec would cost a minimum of Rs.1,20,000/patient whereas the generic drugs already being sold in the market come at a much cheaper price. This would prevent patients from having cheap cancer medication and this according to the Association is totally unfair. The petition is still in study. Till then let us wait and watch.



This is a common problem which arises in India everythime a drug enters Indian Pharma Market. Please tell what would you do if you were the judge hearing this case.

Looking forward for your comments

The birth and the existence of the drug Glivec

In other countries other than India, GLIVEC is a life saving drug for people who suffer with either Chronic Myeloid Leukemia (CML) or Gastrointestinal Stromal Tumors (GSTM). As usual there is this fuss about its sales in India, but I will come back to that later.



But let us see how was Glivec (Imanitib) born



Now when we talk about CML, scientists at University of Pennysylvania detected "Philadelphia Chromosomes" in almost 95% cases of CML, then it was at University of Chicago it was elucidated that this chromosome was a result of reciprocal translocation between chromosome No. 9 and 22. This is a fusion between ABL protoncogene on Chromosome No.9 and BCR(Break Point Cluster region) on chromosome No.22. Later scientists at Whitehead Institute showed that the the protein product of this fusion gene BCR-ABL was a 210 kd kinase phosphoprotein.This protein results in excess and uncontrolled production of White Blood Cells by either inhibiting apoptosis pathways or by increasing cytokine independent growth of cells. This is all mediated by ATP when ATP binds to its site on BCR-ABL kinase protein.

This is where scientists from Novartis came in and finally came out with this compund called Imanitib(Glivec) which binds at the BCR-ABL-ATP pocket preventing ATP's binding to BCR-ABL and so ensuring apoptosis.

Everything whatever I have written seems to be beautiful,short and sweet bed time story,but it isn't .The story of Glivec has not been so easy, its birth has gone through lot of twists and turns. Look down for the timeline of Glivec: