Monday, 18 June 2018

Can this Devil operate miracles? On the anti-inflammatory potential of the harpagophytum procumbens (Devil's Claw)

The World Cup started a few days ago, Mr Kim has met Mr Trump and apparently we are postponing another global armed conflict. I guess we can say the devil is losing this battle and all because our awareness has been raised lately. We are gradually investing in empathy rather than media displays of vulgar superiority. Just help sort out the plastic epidemics by buying less plastic-wrapped products, by demanding a serious environmental consciousness from your wholesalers and from yourself, and we must have a dandy world to show our grandchildren.

Yeah, the devil must not have the upper hand. Unless, of course, we are talking about autoimmune diseases such as Sjogren's syndrome, Lupus, and the whole rheumatic paraphernalia.... and so on and so forth. When it comes to anti-inflammatory issues we must give the devil a chance. OK, now that those who are crazy religious freaks and do not listen/read 'til the end are already painting banners stating God hates homosexuals and bashing biological evolution theories, let's focus on the devil for a moment. But merely on its claw, the Devil's Claw (known by the botanists as Harpagophytum procumbens).

You know, I got one of those emails that is so paradoxical and disturbing (a bit like when Jesse Lee Peterson goes on TV rebranding racism) - bear in mind I haven't taken a stance here. This is not a political blog and I do not dispute idiosyncrasies unless I am asked my opinion on it. But on such occasion the email I was sent explained that this Devil's Claw was the Father of all Miracles and would really fix any Sjogren's, Lupus, Cushing's etc etc etc patients suffering with pain and inflammation to a degree that Hell would become a vast garden of scented flowers.

I had to search the web for articles that would clarify all my concerns and ease my doubts. I ended up finding a video on YouTube, by a certain Dr. James Meschino, that pretty much throws a flaming scare alarm on the lenient use of this plant. Hence, I decided to review a few articles just to be sure that this product can actually be used for treating certain autoimmune diseases with an inflammatory profile. Huge disclaimer here - please ALWAYS resort to your medical doctor or pharmacist for they are the ones who know about your medical history, and use this information for educational support (Each Case Is a CASE!).

In summary this Dr. Meschino states that in fact this native plant from South West Africa, Angola, Madagascar, Botswana, Zimbabwe, Namibia and Kalahari Desert - Devil's Claw - shows enormous anti-inflammatory potential. He says:

1) one of its active constituents is the harpogaside that is believed to be the agent responsible for counteracting inflammation;

2) due to its bitterness it stimulates acid release in the stomach promoting better protein metabolisation;

3) He advises on a quarter to half a gram, two to three times daily (an amount that will roughly correspond to about 5% in harpagoside content);

4) and that harpagosides are believed to hold powerful anticoagulant effects, and for that matter can reactivate or aggravate ulcers, thus should not be combined with other anti-inflammatories (non-steroidal or steroidal ones), nor with anti-coagulants (even if new generation ones). The risk is simple to understand and serious in its own nature - INTERNAL BLEEDING.



Pharmacological active molecules

Not all molecules show the same anti-inflammatory potential, as shown by Fiebich et al (2001) [1] who conducted a very interesting study using a Devil's claw commercial extract to inhibit lipopolyssacharides of bacterial nature. In fact, McGregor et al (2205) [2] also confirmed such, a few years later, when attesting the pharmacological/therapeutic potential of this plant, especially the role of the iridoid glicosides present in its list of constituents (namely harpagoside, procumbide, harpagide, and the 8-para-coumaroyl-harpagide). But warnings were simultaneously published as to the limitations imposed by the test models used.

Toxicity

Well, in regard to toxicity, al-Harbi et al (2013) [3] subjected mice to different official treatment protocols (as suggested by the World Health Organisation): The chronic toxicity study used 100 mg/Kg/day (representing 1/5 of the pharmacologically active dose) administered for a period of 3 months, and focusing on vital organ weight variation, external general symptoms of toxicity, and body weight changes and mortality (up to the end of the trials and not for long-term periods); and concluded that the subjected cohorts experienced low toxicity.

The same study also covered acute toxicity where the subjects were presented to oral doses (0.5, 1 and 3 g/Kg body weight) of the drug suspended in water. This time the analysis focused on autonomic responses, motor activity and central nervous system excitation. One interesting finding is related to 0.5 g/Kg treatment of Devil's claw that  significantly reduced blood glucose levels when compared to untreated cohorts.  However, these were merely preliminary studies and only point towards general assumptions for future studies to consider.

Applications in rheumatic diseases

The incidence of musculoskeletal disorders responsible for disabling many people's lives is high, and any possible natural treatments with pharmacological potential must be analysed for future remedies. Brien et al (2007) [4] compiled a review on the topic that pointed towards safe use of Devil's claw in comparison to non-steroidal anti-inflammatories in reducing pain associated to this disease. The same positive results were also supported by Warnock et al (2007) [5] that focuses their analysis on a number of rheumatic diseases (including arthritis) and a single group of 259 patients for eight weeks with tolerance, liver tests and blood analysis performed. But the main concern could not be answered to, meaning its safe use is still not guaranteed especially because there are no long-term safety assessments and the populations studied are quite limited in number.

Safety

Because I could not find many articles that supported the allegations of Dr. Meschino (I am not saying there isn't any, I am just saying I couldn't find that many) I am not going to say he isn't right. One think I am certain of is that the jury is pretty much still out there on the safety of this plant. But its pharmacological efficacy and range of applications is very much attested. Nevertheless, what the doctors suggest is almost common sense for when we are unaware of the mechanism of action [MOA], as it is the case for the Devil's claw herb, and the MOA of many other complementary and alternative medical therapies [6]. One thing is certain, because of its bitterness it will indeed affect stomach acidity, ergo affecting drugs like proton pump inhibitors, H2-blockers (also known as H2 receptor antagonists) and the like, used to reduce stomach acidity. This is the reason why it might be involved in the worsening of ulcers. However, the safety assessments I was able to find are limited in numbers of populations studied and even range of observations performed. Having said that, I found a really nice piece of document that is 69-pages long, written by the European Medicines Agency [7] (access here) that I will eventually read and try and summarise for you. Bear in mind this document covers many different aspects like medicinal application of this plant, to clinical and non-clinical data, clinical safety, pharmacovigilance aspects and what interests you the most, being the risk-benefit assessment. Once again, after a very brief reading (not thorough at all) I could only find a drug interaction study [8] supporting the allegations of Dr. Meschino, but I still have to lay my eyes properly on this document. The article by Patel et al (2008) [8] apparently (as I could not pay for it, but if you want me to read it just be my guest and send me the money :DDDD) suggests putative interactions with anticoagulants (e.g. warfarin) leading to gastrointestinal bleeding. There was also another article I found (access here) [9] but with no listed authors or free-PDF available that suggests that, in practice reports and concerning devil's claw roots exposed-patients, some showed up with upper gastrointestinal disorders.

The jury is pretty much out there as I already said, but I am sure I will have to discuss the topic further in the weeks to come. Until then, play it safe.

[1] Fiebich, B. L., Heinrich, M., Hiller, K. O., Kammerer, N. (2001). "Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69". Phytomedicine, 8(1), pp. 28-30.

[2] McGregor, G. Fiebich, B., Wartenberg, a., Brien, S., Lewith, G., Wegener, T. (2005). "Devil's Claw (Harpagophytum procumbens): An anti-inflammatory herb with therapeutic potential. Phytochemistry reviews, 4(1), pp. 47-53.

[3] Al-Harbi, N. O., Al-Ashban, R. M., Shah, A. F. (2013). "Toxicity studieson Harpagophytum procumbens (devil's claw) capsules in mice". Journal of Medicinal Plants Research. 7(42), pp.3089-3097.

[4] Brien, S., Lweith, G. T., McGregor, G. (2007). "Devil's Claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a review of efficacy and safety".  The Journal of Alternative and Complimentary Medicine, 12(10).

[5] Warnock, M., McBean, D., Suter, A., Tan, J., Whittaker, P. (2007). "Effectiveness and Safety of Devil's Claw tablets in patients with general rheumatic disorders". Phytotherapy Research, 21(12), pp. 1228-1233.

[6] Setty, A. R., Sigal, L. H. (2005). "Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy and side effects". Seminars in Arthritis and Rheumatism, 34(6)pp. 773-784.

[7] Assessment report of Harpagohytum procumbens DC. and/or Harpagophytum zeyheri Decne, radix. [http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2016/11/WC500216100.pdf]

[8] Patel, J. A., Gohil, K. J. (2008). ""Warfarin-herb interactions: a review ad study based on assessment of  clinical case reporsts in literature". Boletin LatinoAmericano y del Caribe de Plantas Medicinales y Aromaticas, 7(2), pp. pp. 85-99. [https://www.scribd.com/document/293374607/Warfarin-Vitamin-K-Patel-2008]

[9] No authors listed (2013). "Devil's Claw root: Ulcers and gastrointestinal bleeding". Prescrire Int, 22(144), pp. 296. [https://www.ncbi.nlm.nih.gov/pubmed/24600731]

1st image kindly taken from Harpagophytum procumbens - diseases, [http://flipper.diff.org/app/items/6532], last visited on the 18th of June2018.

2nd image kindly taken from Kew, Royal Botanic Gardens, [https://www.kew.org/science/news/plant-story-devils-claw-found-and-collected-from-botswana], last visited on the 18th of June 2018.

Wednesday, 6 June 2018

Pomegranate contamination kills woman in Australia

A cut pomegranate

Image copyrightEPA
Image captionAustralian authorities have linked 24 hepatitis A cases to a frozen pomegranate product
"An Australian woman has died after contracting hepatitis A from a packet of frozen pomegranate.
The 64-year-old died in South Australia last week in a "rare and tragic" case, state health authorities said.
Local officials issued a warning about the Australian-owned Creative Gourmet product in April. It has been linked to 24 cases of hepatitis A nationally.
Australians have been urged to check their freezers and discard packets of the frozen fruit.
About 2,000 packets of the Egyptian-grown pomegranate arils were sold. Fresh pomegranate and locally grown products were not affected, authorities said.
"The woman's death is the only death linked to this recalled product nationally to date," South Australia chief medical officer Prof Paddy Phillips said.
Most other people affected had made a full recovery and no further cases were expected, he said.
Hepatitis A, which attacks the liver, is usually spread through faecal matter, transmitted through sex or by touching contaminated food or objects.
It typically takes between 15 and 50 days to develop symptoms, which include nausea, fever and yellowing of the skin, local health authorities said.
Entyce Food Ingredients has said the contamination was linked to a "a relatively small batch" of its product.
Last year, the company was also forced to pull a selection of its frozen mixed berries products following another hepatitis A outbreak.

Original article on the BBC News website (access here).

The real survival rates to cancer - Part 2 of 3

Following on the first part (see here) where the origins of chemotherapy were briefly discussed, I am here today to present the numbers available on the web and that concern survival rates to cancer. This topic is far from being of a simplistic nature; the disease itself is complicated, multifaceted and generates eruptive emotions. But times have been changing with developments made known that bring new pharmaceuticals to hospitals, better knowledge on disease development and more sensitive predictive technology. Available literature on the matter of survival to cancer is not scarce at all, having said that it is difficult to summarise the enormous lists of sources, references and cited researches that populate the Internet these days.

To better present data in a simplified manner, I decided to generate a summary table where you can find the different categories and the sources used to populate it. Bear in mind that, as expected, this is not an exhaustive compilation of data, but a rough approach to some of the most relevant articles I was able to find with the very limited time I have available these days. I hope that this table can, at least, lead you to the very fine research that is being developed by some important research groups worldwide. Apologies if most of these results are retrospective, but as one can imagine the time it takes for these groups to compile genuine data and make sense of the gathered numbers, discuss these and reproduce meaningful information in the shape of reliable publications, is on its own self-explanatory.

Finally, it would be simpler to just copy-paste incredibly well-put information obtained from websites such as the Cancer Research UK (access here) where a comprehensive and extraordinarily well structured summary of cancer survival rates (for most common cancers) is presented concerning the regions of England and Wales. However, this pool of information comes with many limitations, the first one being the fact that not all countries are represented, and the disease specificity as well as the medical techniques involved are not so well described.

[A]


So to overcome this over generalisation that can be informative to a certain extent, but may lack on a certain identity, I decided to approach this article with a live-table. This table is not amorphous or rigid but a 'tool' that I will be updating whenever I find specific articles that due to their inherent quality and development of a particular treatment analysis represent, in my humble opinion, a good retrospective-or-present indicator of the survival rates associated to a certain population/technique/cancer type/methodology. In addition, this is a nicer method to assess how survival rates have changed through time with the improvements on methodology and technology. And click on the images for better resolution!!!

Please consider this article in constant progression: 



[1] Young, J, L., Ries, L. G., Silverberg, E. et al (1986). "Cancer Incidence, Survival and Mortality for Children Younger than Age 15 Years old". Cancer, 58, pp. 598-602.

[2] Lai, E. C., Tompkins, R. K., Mann, L. L., Roslyn, J. J. (1987). "Proximal Bile Duct Cancer. Quality of Survival". Annals of Surgery, 205(2), pp. 111-118.

[3] Folkesson, J., Birgisson, H., Pahlman, L. et al (2005). "Swedish Rectal Cancer Trial: Long lasting benefits from radiotherapy on survival and local recurrence rate". Journal of Clinical Oncology, 23(24), pp. 5644-5650.

[A] Images kindly taken from Cancer Research UK, Cancer survival for common cancers, [http://www.cancerresearchuk.org/health-professional/cancer-statistics/survival/common-cancers-compared#heading-Two], last visited on the 6th of June 2018, last update unknown.


Thursday, 24 May 2018

Memories might be transferred between generations through DNA

I know research on this matter is still early age, inconclusive and using models that can't be immediately related to humans (at least on the complex epigenetics bridge), but I have discussed this very same topic so many times with my wife. I always tell her - Rubbish DNA my as*, there's definitely a pool of acquired generational memories to unlock, tangled on what we stupidly call Rubbish DNA. Nature is way too sophisticated and tuned to waste energy on something irrelevant. There is always a better explanation for things when the human ego wants to excuse our ignorance on the universe out there and tag the object of our blatant lack of knowledge, of rubbish!!! Calling something we don't know about our genetics, of rubbish, is exactly like looking to the sky on a stormy day where thunder strikes the dry air and cry that the Gods are upset at us for not throwing them an adulation party :P

I still don't have the information to prove my point, but I believe others do share my view on this matter. But maybe this article by Houri-Ze'evi et al (2016) can start a very promising, interesting and much necessary debate. Times are exciting for science, especially for defining our human nature.


Don't mind 'too much' about the content of the video (I am sharing it as a starting point, an entry door to a discussion), I'm not the author but I do share his overall opinion on the matter. However, for the sake of scientific reliability, we all lack on solid proof for consubstantiation of our belief on this matter. But the debate has been triggered, What 'you think?

[1] Houri-Ze'evi, L., Korem, Y., Sheftel H et al (2016). "A tunable mechanism determines the duration of the transgenerationalsmall RNA inheritance in C. elegans". Cell, 165(1), pp. 88-99.

Post image kindly taken from Reset.Me [http://reset.me/story/science-proving-memories-passed-ancestors/].

Wednesday, 23 May 2018

The real survival rates to cancer - Part 1 of 3

It is very difficult for anyone detached from the reality of clinical trials and the research developed by the biggest pharmaceutical companies to have access to secretive data pharmaceutical companies hold on their pipeline products (even when they become fully marketed ones).  We don't necessarily have to initiate or feed any kind of global conspiracy theory. There is huge investment in researching a pharmaceutical product destined to battle diseases as serious as cancer is. Such investment must be claimed back when the product reaches the market and becomes fully or partly available to hospitals, patients, for compassionate use, etc. Not always the different governments support pharmaceutical research to the same extent as governments claim taxation on these companies or impose price cuts/subsidiary support when the products are given market authorisation. 

It is not my job to analyse the soul of said companies as it is not my job to scrutinise the role of governments in the market authorisation and governmental participation process. But for such a global, relevant and recurrent disease that is ever so present in our day-to-day lives (every single one of us has to some extent come across a friend/relative/acquaintance affected by its ramifications) the BIG C is an obscure scenario. Whenever we are forced to bereave upon such frailty, our human side becomes a lot more mechanical, I suppose; a lot more statistical. The positive ones will hold onto the minimum numbers and foresee survival, the negative ones will probably see the opposite side of the mirror. I'm not here to judge, but I tend to be a positive one, and I would want everybody to be positive on their experience with such terrifying disease.

Hence, the idea of "celebrating" about 75 years of the first use of chemotherapy agents in a cancer patient [1] made perfect sense to me. A celebration based on survival, on the numbers that we are to increase but still attribute hope, regardless of how small they can be. 

We are then obliged to mention JD, as he was known back at the Yale Medical Center in 1941 when he was diagnosed with lymphosarcoma (a cancer of lymphocites). The expected treatment would be a combination of radiation and surgical resection. A fast-spreading disease branched through JD's body and the cervical tumours he had been screened for suddenly were unresponsive to radiation and spread to his armpit. His fate was about to be drawn if it wasn't for WWI's nitrogen mustard gas and its associated leukopenia (reduction of white blood cells - leukocytes - in the blood) inducing a low count on those exposed to it.


Well cancer, in very basic terms, isn't but a fast and abnormal multiplication of cells. Therefore, any substance that could attack those sub-systems prone to quick cellular production (hair, immune system, etc) could represent a potential pharmaceutical agent if shown to have reduced toxicity against humans. That wasn't the case for mustard gas, but at least the motto for what would become a very interesting research phase was given the go-ahead flag. And nowadays the common plebeian response to cancer is an immediate word -  chemotherapy. However, statistics are still quite hidden beneath the veil of frailty and business approach that both people (affected by their dramas) and pharmaceutical companies (profiting from the human drama) tend to either ignore, restrict, keep or cherry-pick.

***
I decided that for this post I'd refer only 1 article, the one by Panos Christakis (see below). The reason being the fact that it is a great article that can do wonders for your need for historical feed on how chemotherapy emerged from the shadows of Word War I. How life typically emerges from death and vice-versa, in a strange synergy of an uninterrupted circle. As if life and death weren't; and all we have is a continuum. The referred article deserves your uttermost attention as I believe it to be a great piece of work that instruct us on the chronological process of bringing a clinical and pharmacological product/procedure to life from the unexpected.

Before I leave you today with the premise to what is to be expected with the upcoming two additional posts - namely, the numbers on cancer survival rates (scientifically published), I'd like to share with you an additional motto for me to produce this trilogy of posts. It has to do with my past experience as an interpreter working in the NHS when I came across a cancer patient for the first time. No personal details will obviously be mentioned, but on the next post I will open with this extremely intense experience I lived and how it affected me tremendously... emotionally... and spiritually.

[1] Christakis, P. (2011). "The Birth of Chemotherapy at Yale". Yale Journal of Biology and Medicine, 84(2), pp. 169-172.

1st image kindly taken from The Irish Times [https://www.irishtimes.com/life-and-style/health-family/happy-birthday-75-years-of-chemotherapy-is-worth-celebrating-1.3200991].

2nd image kindly taken from Haiku Deck [https://www.haikudeck.com/history-of-wwi-uncategorized-presentation-546htuF1RC].

Tuesday, 15 May 2018

TheToxicologistToday considered 3rd in the Top 20 Toxicology Blogs on the web

Feedspot, a modern RSS content reader for netizens who want or need to stay up-to-date with the most reliable and interesting content online, have emailed me with special congratulations. It happens that these information minions kindly attributed The Toxicologist Today a third place at the Top 20 Toxicology Blogs (see here). My humble toxicology blog made the podium with a 'bronze medal' that touched my heart, not because of the resonance/repercussion that such might have on my readers' count (if anything that will make me work more seriously towards increasing quality and entice level of my articles), but mostly because someone cared enough to analyse what I have been doing for pure love since August 2010. My small and honest contribution to a world with free scientific information for all - for education and information empower the public. 

Actually, some of the blogs that also made the list are advertised as interesting reads on the side columns of The Toxicologist Today. Some even operate on the realm of Forensic Toxicology, exactly the same area I recently produced a serious game for with SciBoard Games (see here for a short example). This honourable mention, in conjunction with the publishing of my very first digital science serious game "Adna's Lab" (download HERE and read more about it HERE) and the book I am writing on Nosocomial Infections, couldn't be a better bouquet of happiness for me.

I am aware that Feedspot might eventually gain from the fact that all those that made the list will propagate their name to the very four corners of the world (of this worldwide circle squareness), but free information is not easy to maintain or even share. I am more than happy to give Feedspot a hand for their capacity to browse through so many candidates and find value exactly on my work... and with such fierce competition that I am in total awe.


I am humbled, emotional and to a certain degree proud because my scientific passion is surfacing as a valued piece of informational work. I had to read and read and read it over and over again to make sure it wasn't a prank!!!! I thank Feedspot and will do my very best to try and maintain this blog of yours as the reliable source of information on Toxicology that I have been thriving for since 2010. Now go look below for the first 17 names of all blogs that made the top list (I will definitely add all of these links to my 'Interesting Reading column' the moment my professional life allows it).

3. The Toxicologist Today