This morning the Nobel prize in physiology and medicine 2015 was awarded to research on parasites and malaria. Willaim C. Campbell and Satoshi Ōmura share one half for their work on parasites; Youyou Tu gets the other half for identifying new malaria drugs from Traditional Chinese Medicine. I have to eat my hat since I could never imagine something from Traditional Chinese Medicine could be really effective, much less be awarded the Nobel prize, but there it is and I might be more cautious in the time to be.
You have to read the paper of Youyou Tu (2004) where he summarizes his work since his graduation in 1969. It is chemical science starting with material out of the prescription book of Traditional Chinese Medicine. Qinghaosu was the first product they found and that is now chemically modified to give much more potent anti-Malaria drugs.
Whether long-term marijuana smoking has robust effects for the human brain has been a matter of debate. In a paper in PNAS Silbey and colleagus from Dallas, Frisco, and Albuquerque have addressed this question using “multimodal measures in a large group of chronic marijuana” smokers. They claim that marijuna smokers the longer the more have decreasing gray matter in orbitofrotal cortex (OFC).
This part of the brain (citation from wikipedia:)
is considered anatomically synonymous with the ventromedial prefrontal cortex. Therefore the region is distinguished due to the distinct neural connections and the distinct functions it performs.It is defined as the part of the prefrontal cortex that receives projections from the magnocellular, medial nucleus of the mediodorsal thalamus, and is thought to represent emotion and reward in decision making. It gets its name from its position immediately above the orbits in which the eyes are located. Considerable individual variability has been found in the OFC of both humans and non-human primates.
The authors are very cautious to attribute these changes to THC. They also found increased connectivity within the OFC and suggest that the OFC gray matter is more vulnerable to the THC effects.
When you are an endocrinologist you know that hormones are released into the circulation in pulses and that melatonin is only produced in the dark, that glucocortoids concentrations in the blood are high during the night and low during the day, that many hormones have their rhythm. Every hormone has its time, as the prophet sayed.
However, what has not been known until now is that to the same extend more than 40 % of all genes are expressed in a circadian (day long) rhythm. Zhang and colleagues measured in the mouse ( and the might be the only shortcoming of the study ) the gene expression with arrays to determine many gene simultaneously in every hour of the day and night. They found 43 % of all genes expressed in a circadian rhythm. They also determined noncoding RNAs and found 1000 of them cycling.
There are consequences for medicine and therapy: The targets of the top most drugs are expressed all in (specific) rhythms: When a drug like aspirin for example is taken at the wrong time, it would be gone before the target is fully expressed. The scale of this problem seems tremendous. Any pharmaceutical company has to do its home work again. But on the other hand, therapy might become more reliable which would be a large improvement.
The circadian rhythm in the 12 organs analysed are quite different. It might take some time to get used to the thinking that genes in question are not stable during the day but change the level of expression. It will be interesting to follow the aftermath of that paper. The paper is open access and therefore free to everybody.
A doctor in Iowa State University spiked the rabbits he had immunized, with human anti-Hiv antibodies to show that his vaccine was successfull; he was caught and faces now up to 20 years of federal justice, says a report by CNN of yesterday.
Obviously not enough criminal intelligence on the side of this doctor. Still one wonders where he got the human antibodies to spike the rabbits, and whether the test applied did not discriminate human from rabbit antibodies. How the head of department got suspicious? Maybe we will never get answers to these questions?
PNAS this week celebrates 100 years of rabies vaccination by Louis Pasteur and Coworkers which took place already in 1885? We do not understand the counting as such but take the opportunity of the celebration anyhow. (From the editorial, and the featured articles it is not emerging why 100 years.) However, it was an tremendous achievement at that time and should be compared to the situation with the actual Ebola crisis: It took away the fear of fatal danger from the persons dealing with the disease and gave hope to those who were biten by mad animals.
The history of vaccination is dealt with by an nice article of Stanley Plotkin. There are additional papers on social matters of vaccination and one paper on NOD- and Toll-like agonists as adjuvants. These papers are free.
To come back to Ebola and the experimental treatment we mentioned before today 6 patients have been treated 4 improved but 2 have died from Ebola. The fatal rate would thus be 33 % versus 60 to 80 % if untreated. This is from nothing to something. However, this is no vaccination.
This weeks Science features a review (DOI: 10.1126/science.1247391) on induced Pluripotent Stem Cells (PSC) and the treatment of diseases with their help. The disease treated in the paper are hematopoietic maladies, diabetes mellitus, liver diseases, neurological disorders, muscular distrophy and heart diseases.
I was particular interested in diabetes and went to study the article. I was surprised to see that a paper was mentioned where immunotherapy, especially the induction of tolerance, was tried. I have explained the strategy behind in a separate article on this website.
The article, at least for the diabetes part, is highly instructive. You may find it in an University library.
It is remarkable how this pandemy threatens the rules seemingly carved in stone concerning untested medicines. What has been valid before i.e. never to use a medicine until a benefit could be proven is gone en face of the actual crisis. The Science magazine has reacted, too, and has put in the Open Access Paper that were published till now that dealt with Ebola. Among these now free papers is a decription how the rules of the WHO have changed. Martin Enserink from Amsterdam writes very clearly of the change of paradigmata at the WHO. Nice reading!
When the Hepatitis B Virus (HBV) is attacked it remains intracellularly as a covalently closed circular DNA (cccDNA) which can give raise to new viruses. In a Perspective contribution to Science (DOI: 10.1126/science.1252186) Amir Shlomai and Charles M. Rice describe an article by Lucifora et al. (DOI: 10.1126/science.1243462) who found a way to get rid of the cccDNA. These researcher found that interferon-α treatment or action via the lymphotoxin-β receptor activated de-aminination of viral cccDNA which renders the viral DNA inactive and receptive to degradation.
The enzymes triggered in the above described processes are apolipoprotein B mRNA editing enzyme APOBEC3A and APOBEC3B, which only work in conjunction with HBV not HIV. Their presence is necessary in order to elicit a virus depletion in liver cells.
This is good news for 400 Million people infected with HBV since it shows that the virus not only can be kept in charge but eliminated, too.
A News Focus article in Science (DOI: 10.1126/science.344.6180.146 ) reports that the Balkan chronic kidney disease is caused by the weed Aristolochia clematis and its drug aristologic acid. The article is concerned that a chronic kidney disease in Central America which is thought to originate from herbicides or pesticides might be more broadly analysed.
The Balkan disease has a very particular geographic distribution: only in mountain valleys and small elevations. It was thought to originate from the kidney toxin ochratoxin A. The new data show that in specimen of tumours from there as well as from patients who suffered from a disease of A.clematis intoxication which is contain in some Chinese herbal medicine had aristologic acid-DNA complexes. Aristologic acid is now regarded as a tumour inducing drug.
My opinion on this that herbal medicine needs to be regarded with the same scientific zeal that is shown to its brothers in the “Schulmedizin”.
Since the effectivness of Tamiflu has been questioned here a report of 29000 patients where the drug appears to work. „Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.“ Lancet Respir Med 2014.