Modelling,Genome Wide Association Studies and Blog links

Loads of Reading!

Modelling Reviews:

http://www.nature.com/nrg/series/modelling/index.html

Genome Wide Association Studies Reviews:
http://www.nature.com/nrg/series/gwas/index.html

Also a good Nature Molecular Systems Biology blog called Seven Stones:http://blogs.nature.com/sevenstones/

Related articles

• Complete genome of the Tyrolean Iceman (dienekes.blogspot.com)
• Book Review: Nutritional Genomics: The Impact of Dietary Regulation of Gene Function on Human Disease, Ed. by Wayne R. Bidlack (blogcritics.org)
• Scientists perform first Asian genome-wide association study on spine disease (medicalxpress.com)
• Fruit Fly Genome in 3D [Life Lines] (scienceblogs.com)
• New study on Sardinian Y-chromosomes/mtDNA/Y chromosomes (dienekes.blogspot.com)
• Unveiling The Genetic Rosetta Stone (medicalnewstoday.com)

Interesting Blog

An interesting blog on science and biomedicine from a variety of perspectives including PhD students,senior researchers and artists.. http://wellcometrust.wordpress.com/

Fraudulent Scientific Paper?-Theres a Site for that…

Human embryonic stem cells A: Cell colonies that are not yet differentiated. B: Nerve cell.Image via Wikipedia

A new website,aptly named Scientific Red Cards,has been set up  to take  inventory of scientific publications for which research misconduct has been assessed.The database is based on user contributions,with the focus being on fraudulent articles and not scientists.

According to a note in Nature, one in three scientists confesses to having misbehaved in the past three years.Few will forget the case of Woo Suk Hwang,a South Korean stem cell researcher, who in 2006 was found to have falsely claimed to have cloned eleven patient- specific embryos in a scientific paper .The storm that followed  set back the field of therapeutic cloning and eroded public trust in science.However, in a twist if fate, it was later found that Hwang and his team had managed to produce stem cells-just not through cloning-but instead through a process called parthenogenesis.Scientists have long hoped to use parthenogenesis to produce stem cells.

‘In parthenogenesis, an unfertilized egg is stimulated to start dividing as if it had been joined by sperm. It develops for a while under the control of its own DNA. Some species, such as sharks, can reproduce that way. ‘However human eggs can’t develop long enough to make a baby.

In cloning,an egg’s DNA is removed and replaced with genetic material from a person. It is then stimulated, as in parthenogenesis, but it develops under the control of the donor’s DNA rather than its own DNA.

In the discredited 2004 paper, Hwang and his co-authors addressed the possibility of parthenogenesis. They wrote that they couldn’t completely rule it out, but they presented evidence to support their claim of cloning.So what happened? Were they fooled or did they deliberately lie?The answer is that we don’t know and may never know…

References

http://www.scientificredcards.org/content/about

http://www.nature.com/news/specials/hwang/index.html

http://www.msnbc.msn.com/id/20090129/

Further Reading

http://www.msnbc.msn.com/id/10589085/

http://en.wikipedia.org/wiki/Hwang_Woo-Suk#

http://www.the-scientist.com/blog/display/55879/

http://sciyo.com/

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• Representations of the Stem-Cell Cloning Fraud: From Scientific Breakthrough to Managing the Stake and Interest of Science (tc.eserver.org)
• Spain’s first fighting bull clone (news.bbc.co.uk)
• Public Feeling for Science: The Hwang Affair and Hwang Supporters (tc.eserver.org)
• Scientist Creates Life. That’s a Good Thing, Right? (time.com)
• What Animals Have So Far Been Cloned? (blurtit.com)
• The Korean Press and Hwang’s Fraud (tc.eserver.org)
• Ethics experts call for refocus of scientific review to ensure integrity of research process (physorg.com)
• The 10 Most Absurd Scientific Papers (science.slashdot.org)

Ebola-Overview and Recent Discoveries

Transmission Electron Micrograph of the Ebola Virus. Hemorrhagic Fever, RNA Virus.Image via WikipediaEbola

Introduction to Ebola

Ebola haemorrhagic fever (EHF) is a viral haemorrhagic fever and one of the most virulent viral diseases known to humankind.The Ebola virus was first identified in the western equatorial province of Sudan and in a nearby region of Zaire (now Democratic Republic of the Congo) in 1976 after significant epidemics in Nzara, southern Sudan and Yambuku, northern Zaire.

Species of Ebola

The Ebola virus belongs to the Filoviridae family (filovirus) and has five distinct species: Bundibugyo, Côte d’Ivoire, Reston, Sudan and Zaïre. Bundibugyo, Sudan and Zaïre species have all been associated with large outbreaks of Ebola haemorrhagic fever (EHF) in Africa causing death in 25-90% of all clinically ill cases, however Côte d’Ivoire and Reston have not.(4,5)Human infection with the Ebola Reston subtype, found in the Western Pacific, has only caused asymptomatic illness, meaning that those who contract the disease do not get sick (clinically ill).

Symptoms

Ebola has an incubation period (time between exposure and first symptoms appearing) of two to twenty one days.It is is characterized by the sudden onset of fever, intense weakness, muscle pain, headache and sore throat. This is often followed by vomiting, diarrhoea, rash, impaired kidney and liver function, and in some cases, both internal and external bleeding. Laboratory findings show low counts of white blood cells and platelets as well as elevated liver enzymes. (5)

Transmission

The Ebola virus is transmitted by direct contact with the blood, body fluids and tissues of those who are infected with it. Transmission of the Ebola virus has also occurred by handling sick or dead infected wild animals (chimpanzees, gorillas, monkeys, forest antelope, fruit bats).

Treatment

Severe cases require intensive supportive care, as patients are frequently dehydrated and in need of intravenous fluids or oral re-hydration with solutions containing electrolytes.No specific treatment or vaccine is yet available for Ebola hemorrhagic fever. Several potential vaccines are being tested but it could be several years before any is available.(5)

Natural Reservoir of Ebola

The natural reservoir of the Ebola virus is unknown despite extensive studies but it seems to reside in the rain forests of the African continent and in areas of the Western Pacific.(5)A natural reservoir or nidus is the long-term host of the pathogen (infectous agent) of an infectious disease. It is often the case that hosts do not get the disease carried by the pathogen or it is carried as a subclinical infection and so asymptomatic(no apparent symptoms) and non-lethal.Different hypotheses have been developed to explain the origin of Ebola outbreaks. Laboratory observation has shown that bats experimentally infected with Ebola do not die, and this has raised speculation that these mammals may play a role in maintaining the virus in the tropical forest.Extensive ecological studies are currently under way in the Republic of the Congo and Gabon to identify the Ebola’s natural reservoir.(5)

Life Cycle

Pathogeneis Schematic

• Virus attaches to host receptors though the GP (glycoprotein) surface peplomer and is endocytosed into vesicles in the host cell.
• Fusion of virus membrane with the vesicle membrane occurs; nucleocapsid is released into the cytoplasm.
• The encapsidated, negative-sense genomic ssRNA is used as a template for the synthesis ( 3′ – 5′) of polyadenylated, monocistronic mRNAs.
• Translation of the mRNA into viral proteins occurs using the host cell’s machinery.
• Post-translational processing of viral proteins occurs. GP0 (glycoprotein precursor) is cleaved to GP1 and GP2, which are heavily glycosylated. These two molecules assemble, first into heterodimers, and then into trimers to give the surface peplomers. SGP (secreted glycoprotein) precursor is cleaved to SGP and delta peptide, both of which are released from the cell.
• As viral protein levels rise, a switch occurs from translation to replication. Using the negative-sense genomic RNA as a template, a complementary +ssRNA is synthesized; this is then used as a template for the synthesis of new genomic (-)ssRNA, which is rapidly encapsidated.
• The newly-formed nucleocapsides and envelope proteins associate at the host cell’s plasma membrane; budding occurs, and the virions are released. (7)

New Discovery

Researchers at Iowa State University have uncovered how the deadly Zaire Ebola virus decoys cells and eventually kills them.A research team led by Gaya Amarasinghe, an assistant professor of biochemistry, biophysics and molecular biology, had previously solved the structure of a critical part of an Ebola protein known as VP35 (Yiral protein 35), which is involved suppression of the hosts immune system.The results of that research were published in the journal Proceedings of the National Academy of Sciences of the United States of America last January.Amarasinghe and his research team now know how VP35 is able to do it.The current research is published in the current issue of the journal Nature Structural and Molecular Biology and is available as an advanced online publication.(1,2,3)

Mechanism of Ebola Immune Evasion

When most viruses invade a cell, they start to make RNA in order to replicate.When the healthy host cell senses the replicating RNA, the host cell starts to activate anti-viral defenses that halt replication and eventually help clear the viral infections.What Amarasinghe and his group have discovered is that Ebola virus encoded VP35 protein actually masks the replicating viral ribonucleic acid (RNA) by binding itself to short double stranded RNA(dsRNA) which results in the cell not realizing it has an invading virus.Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses. Host mechanisms detect the dsRNA and initiate antiviral responses.(6)

Conserved basic residues in VP35 IID (Interferon Inhibitory Domain)recognize the dsRNA backbone, whereas the dsRNA blunt ends are ‘end-capped’ by a pocket of hydrophobic residues that mimic RIG-I (retinoic acid inducible gene I)–like receptor recognition of blunt-end dsRNA.(1,2)One of the reasons Ebola, in particular the strain isolated from Zaire, is so deadly is that the host cells don’t have any immune response when the virus enters the cell, said Amarasinghe.(1,2)

“The question with Ebola has always been ‘Why can’t host cells mount an immune response against the Ebola virus, like they do against other viruses?’” said Gaya. (2)

“The answer is, ‘If the cell doesn’t know that there’s an infection, it cannot build up any response.’ So our work really gets at the mechanism Ebola infection and immune evasion.(2)

Research

The collaborative approach taken by Amarasinghe enabled him to team up with virologist Christopher Basler at the Mt. Sinai School of Medicine, New York City, to investigate how the structural findings match up with how these proteins function inside the cell.”Our initial structure that we solved in 2008 was key to expanding our knowledge, but the structure was just part of the equation, and when we put it together with the functional studies, everything made sense,” Amarasinghe said.In his current research, Amarasinghe focused on a specific part of the

Phylogenetic tree comparing full-length genomes of ebolavirus and marburgvirus by Bayesian analysis. Posterior probabilities greater than 0.5 and maximum likelihood bootstrap values greater than 50 are indicated at the nodes.

Zaire Ebola VP35 protein that he thought looked unusual.As testing results came in, he found that the suspect region of the protein was binding with, or neutralizing, the part of the host cell that triggers the immune system in the cell. (2)

“The interesting thing about the Ebola virus is that it doesn’t let cells even get started to defend themselves,” he said. “This hides the (viral) RNA from being recognized by the host cell. This is a powerful immune evasion mechanism.” (2)

Other Research Findings

It has also been found that the Ebola virus  disables a cellular protein called tetherin that normally can block the spread of virus from cell to cell.Ebola Glycoprotein (GP) possesses the ability to counteract tetherin, which is both IFN (interferon)-induced in many primary cells and constitutively expressed on the primary targets of Ebola virus infection, particularly monocytes and dendritic cells.Tetherin,also known as Bst-2 or CD317, is one of the immune system’s responses to a viral infection. If working properly, tetherin stops the infected cell from releasing the newly made virus, thus shutting down spread to other cells.(8)Thus when it is antagonized it can no longer block the spread of the virus to other cells.

Ebola also possesses several strategies to antagonize IFN production and signaling. Ebola VP35 prevents IFN production by blocking activation of IFN regulatory factor 3, and VP24 (Viral Protein 24)inhibits IFN responsiveness by blocking the nuclear accumulation of tyrosine-phosphorylated STAT1(signal transducer and activator of transcription 1) . These proteins likely suppress de novo IFN-induced synthesis of viral restriction factors, but constitutive (always on) expression in various cell types remains a restrictive barrier to viral infection. (6,8)

###

Further Information

Amarasinghe, along with Daisy Leung, associate scientist; Mina Farahbakhsh, undergraduate student; Eshwar Ramanan, graduate student; Luke Helgeson, undergraduate student; and Richard Honzatko, professor; all from Iowa State’s biochemistry, biophysics and molecular biology department, together with Kathleen Prins, graduate student, and Basler, associate professor; from Mount Sinai School of Medicine; JoAnn Tufariello; assistant clinical professor of the Albert Einstein College of Medicine, New York City; Dominika Borek, instructor; and Zbyszek Otwinowski from the University of Texas Southwestern Medical Center, Dallas; and Jay Nix from the Berkeley National Laboratory, Calif., co-authored this study.

Work in the Amarasinghe laboratory was funded in part by the Roy J. Carver Charitable Trust, National Institutes of Health, and the Midwest Regional Center for Excellence for Biodefense and Emerging Infectious Disease Research. X-ray crystallographic data were collected at the Advanced Light Source beamline 4.2.2., and the Advanced Photon Source Structural Biology Center Sector 19 beamlines.

Sources

1.Leung,Daisy W, Prins,Kathleen C ,Borek,Dominika M , et al (2010)’Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35′ Nature Structural & Molecular Biology [17 January 2010]  doi:10.1038/nsmb.1765

2.http://www.eurekalert.org/pub_releases/2010-01/isu-isu011910.php

References

3.Daisy W. Leung^a,Nathaniel D. Ginder^a,D. Bruce Fulton^a,Jay Nix^b,Christopher F. Basler^c,Richard B. Honzatko^a andGaya K. Amarasinghe^a1 Structure of the Ebola VP35 interferon inhibitory domain [January 2, 2009], doi: 10.1073/pnas.0807854106

4.WHO ‘Ebola Hemorrhagic Fever’ :http://www.who.int/csr/disease/ebola/en/

5.http://www.who.int/mediacentre/factsheets/fs103/en/index.html

6.Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling.http://www.ncbi.nlm.nih.gov/pubmed/16698997

7.http://biomarker.cdc.go.kr:8080/pathogen/pathogen_view_en.jsp?pclass=2&id=44

8.Rachel L. KaletskyJoseph R. Francica et al (2008)Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein,PNAS,doi: 10.1073/pnas.0811014106

Further Reading

http://www.rcsb.org/pdb/explore/explore.do?structureId=3FKE

http://esciencenews.com/articles/2009/01/27/penn.study.identifies.how.ebola.virus.avoids.immune.system

http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Ebola.htm

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• Embattled pigs source of Ebola virus, too: study (thestar.com)
• Surprise Army Find: 9,200 Vials of Germs (abcnews.go.com)
• Books: Epidemics, Fearsome and Fascinating (nytimes.com)
• Single host gene may hold key to treating both ebola and anthrax infections (scienceblog.com)

C-Reactive Protein (CRP) Gene Variants Not Assscoiated With An Increased Risk of Cancer

A picture of CRP from 1B09.pdb made using pymol;Image via Wikipedia

Introduction

Gene variants associated with increased circulating levels of C-reactive protein, a marker of inflammation, are not associated with an increased risk of cancer, according to a brief new communication published online on January the 7th in the Journal of the National Cancer Institute.(1)

Research

The scientists,Stig E. Bojesen, M.D., Ph.D., of the Department of Clinical Biochemistry, Herlev Hospital, and Copenhagen University Hospital in Denmark, and their colleagues used a Mendelian randomization design (for more information on this see my blog post on Mendelian Randomization) to test whether four common C-reactive protein (CRP) polymorphisms were associated with increased circulating plasma CRP levels and to determine whether this increase was associated with cancer. The study population consisted of 10,215 participants in a prospective study and 36,403 participants in a cross-sectional study of the adult general population of Denmark, all of whom where genotyped for CRP single-nucleotide polymorphisms (SNPs).(1)

C-Reactive Protein

Human C-reactive protein (CRP) (a) is the classical acute phase reactant, the circulating concentration of which rises rapidly and extensively in a cytokine-mediated response to tissue injury, infection and inflammation. CRP, named for its capacity to precipitate the somatic C-polysaccharide of Streptococcus pneumoniae was the first acute-phase protein to be described.(b)The protein resembles an antibody and performs several functions associated with host defence: it promotes agglutination, bacterial capsular swelling and phagocytosis, and activates the classical complement pathway through its calcium-dependent binding to phosphocholine which is expressed on the surface of dead or dying cells (and some bacteria). It is a member of the pentraxin family of proteins.(c)

Research Results

It was found that variants in the CRP gene  were associated with altered plasma levels of CRP but did not find an association between these gene variants and an increased risk of cancer. The authors write that “…although we may be able to exclude CRP per se as a cause of cancer, we cannot exclude the possibility that inflammation could lead to cancer. Also, our results do not invalidate the potential clinical use of slightly increased plasma CRP levels to predict the risk of certain cancer subtypes.”(1)

Research on C-Reactive Protein and Diabetes

Previously Eric Brunner of the Royal Free and University College London Medical School, London, and colleagues, examined the association between levels of C-reactive protein and the risk of type 2 diabetes in a paper published online in PLOS medicine in 2008.(1)

Results

Previous research had suggested that raised levels of this marker are linked with an increased risk of diabetes but it was not clear whether C-reactive protein actually caused the condition.Brunner and colleagues used Mendelian randomization to account for the effect of other variables (such as obesity, blood pressure, and socio-economic position) which might play a role in the development of diabetes.The researchers showed that levels of C-reactive protein in the blood are not likely to cause diabetes but noted that inflammation may play a causal role via upstream effectors rather than the downstream CRP.(2)

Sources:

1. Allin KH, Nordestgaard BG, Zacho J, Tybjærg-Hansen A, Bojesen SE.(2010)

‘C-Reactive Protein and the Risk of Cancer:A Mendelian Randomization Study’,available: http://jnci.oxfordjournals.org/cgi/content/abstract/djp459v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=snps+in+c+reactive+protein&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

2. Brunner EJ, Kivimäki M, Witte DR, Lawlor DA, Smith GD, et al. (2008) Inflammation, Insulin Resistance, and Diabetes—Mendelian Randomization Using CRP Haplotypes Points Upstream. PLoS Med 5(8): e155. doi:10.1371/journal.pmed.0050155

3. Keavney B (2008) More Evidence Against a Causal Association between C-Reactive Protein and Diabetes. PLoS Med 5(8): e174. doi:10.1371/journal.pmed.0050174

References:

a. HUMAN C-REACTIVE PROTEIN COMPLEXED WITH PHOSPHOCHOLINE http://www.rcsb.org/pdb/explore/explore.do?structureId=1B09

b.Mark B. Pepys and Gideon M. Hirschfield (2003) C-Reactive protein:a critical update ,J. Clin. Invest. 111(12): 1805-1812 (2003). doi:10.1172/JCI18921.

c.EBI search for ‘pentraxin’ http://www.ebi.ac.uk/ebisearch/search.ebi?db=proteinFamilies&t=pentraxin

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• C-Reactive Protein – What’s All The Hype About? (blogs.webmd.com)

Mendelian Randomization: A Brief Overview

Introduction

I’ve seen the term Mendelian randomization in a few articles and their related papers that I’ve read recently ,and not knowing what it was I’ve written this overview to teach myself and tell anyone else who doesn’t know.

Genetic Epidemiology

Geneticepidemiology is concerned with understanding the heritable aspectsof disease risk, individual susceptibility to disease, and ultimatelywith contributing to a comprehensive molecular understandingof pathogenesis.(2) Epidemiologists look for modifiable causes of common diseasesto improve population health. However, epidemiological studiesmay identify spurious “causes.” For example, the epidemiologicalfindings that hormone replacement therapy protects against coronaryheart disease and that carotene prevents lung cancer have been refuted by randomized controlled trials,raising concerns about the value of epidemiological studies. The misleadingfindings were thought to be due to confounding by behavioral, physiological,and socioeconomic factors related both to exposures and to diseaseend points. One solution to these problems is mendelian randomization. (3)

What is Mendelian Randomization?

Mendelian randomization is a recent development in the field of genetic epidemiology which uses non-experimental studies to examine the causal effect of a modifiable phenotype or exposure on disease by making use of measured variation in genes of known function.It is based on Mendel’s second law that inheritance of one trait is independent of inheritance of other traits.If we know of a gene closely linked to the phenotype without direct effect on the disease, it can be reasonably assumed that the gene is not itself associated with any confounding factors.(2,3)

Mendelian Randomization Approach

In the Mendelian randomization approach, investigators first identify genetic polymorphisms that affect levels of the risk factor whose causal significance is queried .  The relationships between polymorphisms and risk factor, risk factor and disease, and polymorphisms and disease are then quantified. If the hypothesised risk factor causes disease, it is anticipated that the association between the polymorphisms and disease risk will be at least commensurate with what would be “expected,” given the association between the polymorphisms and the risk factor, and the association between the risk factor and disease.Mendelian randomization provides a potential method to assess the causality of associations described in epidemiological studies where suitably specific drugs to undertake randomised controlled trials are not yet available.(1)

Limitations

Some limitations include a lack of suitable genetic variants, unreliable associations, population stratification, linkage disequilibrium (LD), pleiotropy, developmental canalization, the need for large sample sizes and some potential problems with binary outcomes.  Given an inheritance of gene expression from parents, Mendelian randomization studies not only need to assume a random distribution of alleles in the offspring, but also a random distribution of epigenetic changes (non-Mendelian, heritable changes in gene expression not accompanied by alterations in DNA sequence) at conception, in order for the core assumptions of the Mendelian randomization methodology to remain valid .(4)

Further Reading

• Davey Smith G. Capitalising on Mendelian randomization to assess the effects of treatments,available: http://www.jameslindlibrary.org/trial_records/20th_Century/1990s/gray/gray-commentary.html
• Mendelian randomisation: Inferring Causality in Observational Epidemiology: http://www.genestat.org/index.php?n=GeneStat.MendelianRandomisation

References:

1. Didelez,Vanessa and Sheehan,Nuala (2007) Mendelian randomization as an instrumental variable approach to causal inference,available:http://smm.sagepub.com/cgi/content/abstract/16/4/309

2. Davey Smith,George and Ebrahim,Shah ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? ‘Int. J. Epidemiol. 32: 1-22.

3.Davey Smith,George and Ebrahim,Shah ,What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ  2005;330:1076-1079 (7 May), doi:10.1136/bmj.330.7499.1076

4. Ikechukwu U Ogbuanu, Hongmei Zhang and Wilfried Karmau (2009) ‘Can we apply the Mendelian randomization methodology without considering epigenetic effects? doi:10.1186/1742-7622-6-3

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Looking for Drug Information?

Image via WikipediaIntroduction

Introduction

I’m writing this post to give advice and include a list of links that I think will be helpful to any college students,businesses,individuals etc who have assignments on various drugs and their manufacturing to do. I know from experience it can be hard to find the exact information you are looking for and nearly impossible to find manufacturing processeses as the details of are generally closely guarded by the drug manufacturers.

Difference Between Generic and Patented Drugs?

One of the first things you may have to figure out is if your drug is still covered by a patent or if the patent has expired and it has now become an off-patent generic drug i.e. many different companies can make the same drug under different trade names.However don’t get confused into thinking a drug is a generic drug  if you see the phrase ‘generic name’ on websites.All drugs have generic names or International Non-Proprietary names (INN‘s),issued by the World Health organization (WHO), which are  the standard names for each drug.INN names are designed to be unique and distinct so as to avoid confusion in prescribing. A similar role is played in Chemistry by IUPAC names to name chemicals in a standard format.

For example,say you are looking for a drug called Panadol. Panadol is a proprietary name i.e. a name owned by someone, for the drug paracetamol which is a generic/INN name.In the United states paracetamol’s non-proprietary generic name is acetaminophen.The American name is known as the United States Adopted Name (USAN).USAN’s are the non-proprietary names that are assigned to pharmaceuticals marketed in the United States.

In summary,the generic name of Panadol is either paracetamol or acetaminophen based on where in the world you are (they are both the same drug).It is an off-patent drug/generic drug (as opposed to an on-patent/proprietary drug) and so it can be manufactured and sold by different companies (since the patent has expired) under various band names such as Panadol,Tylenol,Dolprone,Calpol, and a whole host of other names (see here for a list of paracetamol brand names on Wikipedia).It is also just sold under its generic names which are paracetamol or acetaminophen;it dosen’t have to be sold under a proprietary name.Other generic names for paracetamol are n-acetyl-p-aminophenol and p-acetamidophenol. Knowing the chemical name,other generic names and the formula of a drug are also useful for searching patents.

Sources of Information

Search Engine

Doing a general search using the tradename and then the generic name on search engines like google is a good first port of call.If the drug is marketed under more than one name its a generic drug,if not it is likely to be a drug still covered by a patent although make sure you havent missed any tradenames by accident.

FDA and EMEA websites

If the drug is approved for use in the U.S. and is a generic it will be on the FDA‘s list of generic drugs on their website which is updated on a quarterly basis.The Europen Medicines Agency(EMEA) ,which is the E.U equivalent of the FDA in America, publish European Public Assesment Reports(EPAR’s) on their website which contain summarys and detailed discussions on drugs approved in the E.U. (access list of EPAR’s here).The Scientific Discussions they publish as part of these EPAR’s are also particularly useful as they often contain a brief section on manufature and quality control tests that will be ran on the drug as well as clinical trial data and pharmacology.Just click on the link for the drug you want to learn more about and then click on the individual icon under your selected language (EN) to read the contents.

The ‘Orange Book’

The ‘Orange Book’ is another resource that is available to search on the FDA website (access here) and it can be searched by active ingredient,patent holder, proprietary name,applicant holder and application number.It will provide information on a multitude of different dose forms of various drugs as well as whether or not the drug is on an unexpired patent (propitierary) or not (generic).

Prescribing Information

Getting the Prescribing Information of a drug is also a must,many sites like Rxlist.com provide this kind of data or it can be found on the website of the drug or the company website.

Product Monograph

Product monograhs are a great information source and will often contain more than the prescribing information.However they can be harder and sometimes impossible to find!Good places to start looking are the website of the drug,the company website,by typing the name into google with the words ‘monograph’ or ‘product monograph’ after it.The AHFS website also publishes a book called AHFS Drug Information which describes many drugs.

Pharmacopeias

Pharmacopoeias are a good source of well referenced drug information and iclude data on toxicology,pharmacology ,uses,physical and chemical data and tests to identify the drug.

Patents

For information on the manufacture of a drug you are in most cases going to have to find the patent or patents for the drug.Good places to start looking are the ‘advanced search’ sections of Free Patents Online,Google Patents and patent abstracts at the EBI.If searching by company name (assigne name),check first to see if the company was previously called anything else or it the the company that now sells the drug acquired the company that holds the patent.If any other company names are associated with the drug search these too.Don’t forget to look at related patents too;these are named on the title page of the patent usually and will be referenced in the text also.

Many of the websites named in this text are also listed in my ‘Resources’ links for ease of access.If anyone knows any other resources that they think would be of use to others,please leave a comment about them!

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Biochemistry Questions Site

Great site for medical biochemistry students and also those doing general biochemistry.Aside from the more serios side it also features fun puzzles,crosswords and trivia sections!

http://biochemistryquestions.wordpress.com/

A Selection of Biochemistry Resources

Image by BlueRidgeKitties via Flickr

Online Biochemistry Hypertext Book:

http://themedicalbiochemistrypage.org/

A Manual for Biochemistry Protocols:

http://www.scribd.com/doc/24872331/A-Manual-for-Biochemistry-Protocols

Medical Biochemsitry Book:

http://www.scribd.com/doc/18252344/Medical-Biochemistry

Magazine on Biopharmaceutical manufacture:

http://biopharminternational.findpharma.com/

Merck Manuals Online:Genetics

http://www.merck.com/mmhe/sec01/ch002/ch002a.html

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