Sunday, February 28, 2016

Call for Articles

We are please to inform you all that, very soon we will be ready for next issue, it is our pleasure to invite you to contribute your best knowledge and research. Your contribution will help us to establish a high standard.
The Annals of Clinical Chemistry and Laboratory Medicine (ACCLM) accept contributions within clinical chemistry/biochemistry and laboratory medicine. This includes clinical biochemistry, clinical molecular biology, hematology, immunology, microbiology, drug monitoring and analysis, evaluation of diagnostic markers, new reagents, reference materials, reference values, and quality in laboratory medicine from all countries. Included in the publishing programme are Original Articles, Reviews, Short Case report, and Letters to the Editor. 
ACCLM, is a Peer reviewed biannual Journal, now indexed in Scientific Indexing Service (SIS), NepJOL, Google Scholar,Indian Science Publications and CNKI Scholar. We are now in the process of indexing in cite factor and Science Citation Index. 
We are now accepting manuscript through online submission system as a part of a better editorial office process and efficient journal management. 
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Executive Editor

Researchers create compound that combats drug-resistant malaria parasites, spares human cells

Bruce Goldman is a science writer for the medical school’s Office of Communication & Public Affairs. Email him at

Stanford University School of Medicine investigators have designed a compound that kills the parasitic microorganisms responsible for malaria but avoids harming human cells.
The compound exploits tiny structural differences between the parasitic and human versions of an intercellular protein-recycling machine called the proteasome.
Malaria, one of the world’s most devastating infectious diseases, exacts a yearly toll of more  than 400,000 deaths, mostly of children younger than 5. Mortality rates are dropping because of large-scale global intervention efforts, but malaria’s prevalence remains stubbornly high, with hundreds of millions of people newly infected each year in sub-Saharan Africa and Southeast Asia. 
Some 2.3 billion people — one-third of the Earth’s people — are at risk for infection with the parasite.

Bloods cells pillaged

Malaria is caused by protozoans of the genus Plasmodium. Five different species of Plasmodium are known to cause malaria in humans, with most deaths caused by one species, P. falciparum. Transmitted by mosquitos, the microbes invade the body, first holing up in the liver and then penetrating and replicating in red blood cells, which they ultimately destroy as they break out in search of new red blood cells to pillage.
“This penetration/replication/breakout cycle is rapid — every 48 hours — providing the opportunity for large numbers of mutations that can produce drug resistance,” said Matthew Bogyo, PhD, professor of pathology. Consequently, several generations of antimalarial drugs have long since been rendered useless, he said.
Resistance to current front-line antimalarial drugs, known as artemisinins, is spreading and has been observed in a half-dozen Southeast Asian countries. But in a study to be published Feb. 11 in Nature, Bogyo and his colleagues showed, using laboratory-adapted clinical samples from Southeast Asia, that the new compound can effectively kill artemisinin-resistant malaria parasites and that low doses of the drug can further sensitize them to killing by artemisinin.
Bogyo shares senior authorship of the study with Paula da Fonseca, PhD, of the MRC Laboratory of Molecular Biology in Cambridge, UK. The lead author is Stanford graduate student Hao Li.

Protein chewers

Proteins, which perform the vast majority of the work done inside a cell, are assembled from building blocks called amino acids, which are linked together in a linear sequence like beads in a necklace. 
The proteasome, a barrel-shaped cluster of proteins, chews up other proteins by breaking those amino-acid links. Proteasomes abound in all human cells and in all protozoans. They are crucial to the elimination of faulty proteins and to cell replication. So blocking their function wreaks havoc within a cell. 
But compounds previously found to block proteasome activity in P. falciparum have tended to inhibit the human version of the proteasome, too, resulting in toxicity that would be unacceptable in a malaria drug. 
In the new study, the Stanford team produced highly purified preparations of both human and P. falciparum proteasomes and then “fed” those two preparations a set of protein fragments collectively containing a vast variety of amino-acid linkages “in order to see which amino-acid linkages these proteasomes like to chew up,” Bogyo said.

Clogging up the works

The team identified 117 amino-acid linkages that are readily chewed up by P. falciparum proteasomes but not so well by human proteasomes, and 153 where the reverse is the case. They used this information to design tiny protein snippets that failed to interact with human proteasomes but that, instead of getting chopped up by P. falciparum proteasomes, would gum up parts of them responsible for cleaving certain amino-acid links.
“They just stick and don’t get released,” Bogyo said. The clogged catalytic sites are now unable to break apart the linkages they were designated to cleave.
Next, the UK group investigated the basis for this selectivity by using a high-resolution version of electron microscopy to map the detailed structure of the parasite and human proteasomes. This allowed Bogyo’s team to optimize the protein snippets they were using as parasite-selective proteasome inhibitors. The three-amino-acid snippet they ultimately focused on, called WLL, was able to gum up two different catalytic regions in P. falciparum proteasomes without any effect on those of cultured human cells. There was a 600-fold difference in WLL’s potency at killing the parasitic cells over the human cells.

Reducing parasites in mice

In experiments with mice with a murine version of malaria-inducing Plasmodium, the researchers saw a nearly complete reduction of parasites with both single and multiple doses of WLL. Still other tests, performed on artemisinin-resistant parasites infecting human red blood cells in laboratory cultures, suggested that the WLL compound was equally effective at killing artemisinin-resistant parasites and artemisinin-sensitive parasites. 
Bogyo pointed out that the artemisinin family of drugs work by modifying proteins in the parasite. Resistance occurs when the parasites’ proteasomes are able to recycle those modified proteins. But this means that artemisinin-treated parasites are particularly sensitive to disruption of normal protein function.
“The compounds we’ve derived can kill artemisinin-resistant parasites because those parasites have an increased need for highly efficient proteasomes,” he said. “So, combining the proteasome inhibitor with artemisinin should make it possible to block the onset of resistance. That will, in turn, allow the continued use of that front-line malaria treatment, which has been so effective up until now.”
Clinical trials of compounds derived from this research remain several years away, Bogyo cautioned.
Other Stanford co-authors are postdoctoral scholars Wouter van der Linden, PhD, Euna Yoo, PhD, and Ian Foe, PhD. 
Researchers from the University of California–San Francisco and the University of Melbourne in Australia contributed to the study.
The study was funded by the National Institutes of Health (grants R01AI078947 and R01EB005011); theMedical Research Council in the UK; Singapore’s Agency of Science, Technology and Research; and theNetherlands Organization for Scientific Research.
Stanford’s departments of Pathology and of Chemical and Systems Biology also supported the work.

Simple new blood test detects TB - and can spot which patients are infectious

A simple blood test  that accurately diagnoses active tuberculosis could save hundreds of thousands of lives each year, experts said today.
The test makes it easier and cheaper to control the disease, which claims 1.5 million lives across the globe annually.
Researchers at Stanford University School of Medicine identified a gene expression 'signature' that distinguishes patients with active traces of TB, from those with either latent TB or other diseases.
The technology fills a need identified by the World Health Organization, which in 2014 challenged researchers to develop better diagnostic tests for active TB.
Globally, TB infects 9.6 million new patients each year, and kills 1.5 million.
Yet the disease remains difficult to diagnose.
Dr Purvesh Khatri, assistant professor of medicine at Stanford, said: 'One-third of the world's population is currently infected with TB.
Even if only 10 per cent of them get active TB, that's still three per cent of the world's population - 240 million people.
Traditional diagnostic methods, such as the skin prick test and inferferon assays, cannot separate patients with active TB, from those who are no longer sick or have merely been vaccinated against TB - most countries vaccinate against the disease.
These older diagnostics can miss a case of TB in patients with HIV.
A common way to test for TB is to look for the disease-causing bacteria in saliva samples, coughed up by patients.
But, it can be hard for people to produce sputum on demand, said research associate Dr Tim Sweeney, one of the authors on the paper.
'If someone can't produce adequate sputum, or if you have a kid who can't follow directions,' it is hard to diagnose them, he said.
 And the test is almost useless for monitoring how someone is responding to treatment, he added.
 As a patient starts to recover, they cannot produce sputum for the test. 
 The new blood test, developed in Dr Khatri's lab, works on an ordinary blood sample and removes the need to collect sputum.
 It can signal a TB infection even if the individual also has HIV.
And, it won't give a positive response if someone only has latent TB or has had a TB vaccine.
It also doesn't matter which strain of TB has infected a person, or even if it has evolved resistance to antibiotic drugs.
The test also works in both adults and children.
The WHO has called for a test that gives a positive result at least 66 per cent of the time, when a child has active TB.
Dr Khatri's test is 86 per cent sensitive in children, researchers said.
And if the test comes up negative, it is right 99 per cent of the time.
That is, of 100 patients who test negative with the Khatri test, 99 do not have active TB.
Developers say the test is simple, and can be done under relatively basic field conditions in rural and undeveloped areas of the world.
In addition, any hospital will be able to perform the test.
When pathogens infect the cells of the body, the infection sets off a chain reaction that changes the expression of hundreds of human genes, the researchers explained.
Dr Khatri's team identified three human genes, whose expression changes in a consistent pattern, revealing the presence of an active tuberculosis infection.
The team validated the new three-gene test in a separate set of 1,400 human samples from 11 different data sets, thus confirming the diagnostic power of the test.
Researchers said the new test not only accurately distinguishes patients who have active TB, it could also be used to monitor patients to see if they are getting better and how well they are responding to different treatments.
Therefore, it can be used not only for diagnosing the disease, but also to help doctors choose the best treatment plan.
Dr Khatri has already begun collecting funding to develop the test for widespread use, both to diagnose TB in patients and to monitor recovery in clinical trials, allowing for more rapid development of better and cheaper treatments. 
The study was published in Lancet Respiratory Medicine. 

Annals of Clinical Chemistry and Laboratory Medicine (ACCLM)

Annals of Clinical Chemistry and Laboratory Medicine (ACCLM) is an official Journal of Nepalese Association for Clinical Chemistry. ACCLM is a peer-reviewed, biannual journal. ACCLM includes original articles, review articles, short communications, letters to the editor, case studies, medical education and current issues.
The scope of ACCLM includes but is not restricted to clinical chemistry, molecular biology and genetics, immunology, therapeutic drug monitoring and toxicology, endocrinology and metabolism, laboratory management and quality assessment, medical education, laboratory medicine with the focus on analytical and clinical investigation of laboratory tests in humans used for diagnosis, prognosis, treatment, and monitoring of disease.