Sugar to fight against Hospital infections!!

Sugar to fight against Hospital infections!!

Posted in Articles

No comments

By Unknown

A Carbohydrate found on the surface of one of the most virulent strains of Clostridium Difficile has been synthesized by scientists in Germany.
This piece of research can prove to be an important breakthrough in the Vaccine development programme against the infection.

C.Difficile bacterium

C.Difficile is a species of Gram-positive bacteria of the genus Clostridium that remains in a dormant form (i.e. spores) inside the colon until a person pops an antibiotic pill. The antibiotics in its course of action also destroys the normal gut flora(the good bacteria) leading to an overgrowth of C. difficile, which flourishes under these conditions. This results in the C.difficile getting converted into its active form and producing toxins which damages the gut wall, resulting in bloody diarrhoea and pseudomembraneous colitis.


C.difficile infections are one of the most common Nosocomial infections worldwide and are the leading cause of death in elderly and those with weakened immune system.Peter Seeberger, who led the team that carried out the research at the Max Planck Institute of Colloids and Interfaces, Potsdam was qouted as saying"C. difficile is on the rise in industrialised countries.There is a need for a vaccine but it's a big challenge."


Treatment with antibiotics is not so effective because of increasing resistance and tough nature of bacterial spores..The majority of severe infections are caused by just one hypervirulant strain - type 027.


To fight this particular strain, Seeberger and his team synthesised the repeating unit of a carbohydrate -pentasaccharide PS-1 - that is only found on the surface of type 027. The linear synthesis involved using one precursor molecule to make four different building blocks, making an efficient process.Their aim is to use PS-1 to create a vaccine to enable the immune system to recognise it, make antibodies against it and mount a response against the infection.

'It is elegant chemistry and shows that if you master the challenges of synthetic carbohydrate chemistry, you can produce something that's medically useful,' says Gerd Wagner, a medicinal chemistry expert at King's College London, UK, who agrees that the research 'opens the door to exploring a vaccine candidate'. 

Seeberger's team was also the first to synthesize PS-2, a carbohydrate found on all strains of C. difficile. He states the possibility of 'combining PS-1 and PS-2 in a single vaccine candidate for better coverage'. His team has begun tests using PS-1 attached to a protein carrier to determine whether animals can create antibodies against it. It will be years before a vaccine is available, he says, but he emphasizes that PS-1 and PS-2 are both promising candidates!!

Vaccine for Brain Tumor: A New Height in Personalized Medicine

Vaccine for Brain Tumor: A New Height in Personalized Medicine

Posted in Articles, brain tumor, clinical trials, heat shock proteins, HSPPC-96, personalized medicine, vaccine

No comments

By Unknown

Developing a Vaccine produced from a patient's one's own tissues has definitely taken Pharmacogenomics-popularly known as "Personalized medicine" to a new height in the present scenario.

The concept of Pharmacogenomics deals with the genetic variation among the masses, and using the genetic data to select the right drugs to treat disease in a given patient. Although at a primary level, this can help the doctors in avoiding pointless treatments and reducing adverse drug reactions in the concerned patients.

Using a patient's own tissues for developing a Vaccine, is in itself a novel strategy employed by Valley Hospital in Ridgewood, N.J, wherein they are offering patients with newly diagnosed glioblastoma multiforme (GBM) (brain tumor) the opportunity to take part in the clinical trials.

The phase II trial, headed by principal investigator and researcherAnthony D'Ambrosio, M.D., director of Valley's neuro-oncology disease management team, is designed to evaluate safety, survival and immune response in patients treated with a heat shock protein peptide-complex vaccine (HSPPC-96) derived from each patient's specific tumor cells.

"Heat shock proteins are believed to play an essential role in helping the immune system to recognize and eradicate diseased cells," said D'Ambrosio.

The Glioblastoma Vaccine study is sponsored by the University of California, San Francisco, and is currently available in limited locations across the country. The study is currently searching for participants who are newly diagnosed, over age 18 and whose tumors have not been excised.

These trials indicate a new era in healthcare with the advent of personalized medicines, for the common good of humanity.

Naming the Antibiotics: Some Intriguing Facts

Naming the Antibiotics: Some Intriguing Facts

Posted in Antibiotics, Articles

No comments

By Unknown

An entertaining and brief but fully documented review of the methods by which discoverers of antibiotics have chosen names for them is given byD. Perlman of the School of Pharmacy, University of Wisconsin. 

Antibiotics named after Organisms: 

Some of the best known, and a total of about 500, have names derived from the organisms producing them, either that of the genus (penicillin, streptomycin, cephalosporins) or of the species (griseofulvin from Penicillium griseofulvum). A few, such as staphylomycin and gramicidin, denote not the source but the organisms susceptible to them.

Antibiotics named after Places:

These antibiotics are named after the geographical sources of the soil where the producing organism was cultivated.

Pimaricin, a useful antifungal antibiotic was named after Pietermaritzburg, near which the soil yielding Streptomyces natalensis was collected.

Nystatin, is the only antibiotic named after the institution in which it was isolated, the laboratories of the New York State Board of Health.

Antibiotics named after people:

1Bacitracin-- Margaret Tracy being the child with a compound fracture from whose wound the producing Bacillus was isolated, where its growth was apparently contributing to overcoming septic infection.

2Helenine, an antibiotic of no clinical value but having an interesting action on some virus infections in mice, was so named by the late R. E. Shope after his wife Helen, because he found the mould producing the antibiotic growing on the cover of a photograph of her which he was carrying while serving in the war in the Pacific.

3saramycetin (a sulphur-containing peptide with systemic antifungal activity) was named  after a mother-in-law.

Antibiotics with Peculiar Names

Public Domain Databases for Medicinal Chemistry

Public Domain Databases for Medicinal Chemistry

Posted in Articles

No comments

By Unknown

Here's a useful overview of the public-domain medicinal chemistry databases out there. 

BindingDB (quantitative binding data to protein targets).

ChEMBL (wide range of med-chem data, overlaps a bit with PubChem).

PubChem (data from NIH Roadmap screen and many others).

PDB (repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids

Binding MOAD (literature-annotated PDB data).

ChemSpider (26 million compounds from hundreds of data sources).

DrugBank (data on 6700 known drugs).

GRAC and IUPHAR-DB (data on GPCRs, ion channels, and nuclear receptors, and ligands for all of these).

PDBbind (more annotated PDB data).

PDSP Ki (data from UNC's psychoactive drug screening program)

SuperTarget (target-compound interaction database).

Therapeutic Targets Database(database of known and possible drug targets).

ZINC (21 million commercially available compounds, organized by class, downloadable in various formats).

Breakthrough Research: Cure for Morphine Addiction found!!

Breakthrough Research: Cure for Morphine Addiction found!!

Posted in Articles, Morphine addiction, opioids, TLR-4 receptor, toll-like receptors. cure for heroin addiction

No comments

By Unknown

In a major breakthrough by a group of Australian scientists, a cure has been found for morphine and heroin addiction which will prove a boon for more than 12 million drug addicts worldwide.(1)

Scientists at the University of Adelaide have identified an immune receptor TLR-4 which is responsible for the drug addiction, and found a way to block this receptor without affecting pain relief.

This discovery can have wide implications as it offers the possibility of using Morphine as a pain reliever without worrying about its addictive properties. The use of morphine and other opioids is currently restricted as it can lead to some harmful effects if addicted to it. 

Morphine and other opioids are known to bind to the opioid receptors in the brain, which results in pain relief and also activation of the "Reward Pathway". This "Reward Pathway" is a result of the release of large quantities of Dopamine in the brain which is the root cause for addiction to opioids.

TLR-4 is a toll-like receptor whose role is to identify  foreign bodies, 
and thus launch an immune attack against harmful pathogens.

The observation that the opioids also bind to the toll-like receptors TLR-4, eventually led the Hutchinson team to the hypothesis, that TLR-4 may act as an amplifier for award when opioids are bound to it. They performed a series of experiments pertaining to the addictive behaviour in rats, by administering a known drug (called plus naloxone- which is known to block TLR-4), and hence blocking the immune receptors. 

Rats given plus-naloxone before receiving morphine did not exhibit behaviour linked to addiction. Their brains also showed a significantlylower release of dopamine than in rats that only received morphine. Using a heat sensitivity test, the team also showed that the rodents given plus-naloxone still experienced pain relief from the morphine, despite lacking signs of addiction.

The idea that the rewarding effect of opioid drugs is potentially mediated by this receptor "flies in the face of current opinion," says Chris Bailey, a pharmacologist from the University of Bath in the UK. "People for hundreds of years have been trying to come up with an opioid analgesic which isn't rewarding," he says.
These findings are particularly interesting, he says, because it's the first time a mechanism has been identified that separates the pain relief and reward responses to opioid drugs. "It has always been seen that the analgesia and the rewarding aspects go hand in hand," he says.

 The National Institutes on Drug Abuse in U.S is further developing the drug to test in clinical trials. As a result, Clinical trials would soon be underway in the coming 2 years, Dr. Hutchinson said.

If the clinical trials were successful, opioid drugs used to relieve pain could potentially be co-formulated with the additional drugs( TLR-4 Blockers) to limit the chance of addiction.

It would also benefit the addicted patients who are admitted in hospital, and require pain relief. Addicted patients require higher doses of the drug, as they are higly tolerant to the drug, so this combination may help in lowering the doses given to the patients.


As bright as it looks, this "potential cure" for morphine addiction can definitely bring a paradigm shift if it passes the clinical trials successively. Hope it happens!!

References: (1) The World Drug Report, 2011 available online at http://www.unodc.org/documents/data-and-analysis/WDR2011/World_Drug_Report_2011_ebook.pdf
(2) for more info on Toll-like receptors, log onto: http://www.sinauer.com/pdf/nsp-immunity-3-10.pdf
(3) for more info on Reward pathways, visit: http://lilt.ilstu.edu/vfdouga/P331/ARTICLES/role%20of%20dopamine%20in%20reward%20and%20pleasure.pdf and http://learn.genetics.utah.edu/content/addiction/drugs/