Microbiology in Forensic Medicine

Microbial forensics is the study area that applies knowledge on microbiology to the challenges of forensic medicine, resulting promising but far from universal acceptance. Notwithstanding, this relatively novel sub-domain of medicinal forensics has laid grounds for an encouraging partnership that, due to its short existence, is in need of globalised methodological standardisation (1, 2). Once a consistent globally accepted set of guidelines emerge, its associated tools and paradigms will become as ubiquitous as microorganisms themselves. Microorganisms will then be providing reliable traceable evidence, crucial in the investigational process, be it in the course of a crime enquiry (3, 4), as an attempt to control the widespread of an epidemic (e.g., the recent tracking of coronavirus outbreak to patient zero and its point source), or even as pointers towards the most adequate treatment response when time is a constraint (5).

It is undeniable that microorganisms are becoming increasingly relevant in Forensic Medicine as professionals in the area build a more robust understanding of the intrinsic specificities of microbiomes, particularly due to the present capabilities of the biomolecular technologies at their disposal (6). Polymerase chain reaction (PCR), quantitative PCR (qPCR), fluorescent dyes and genetic probes, etc, individually or combined, empower the investigator, even when samples are minute or almost inexistent (7).

But what exactly makes the case for microbial forensics as a reputed science? The answer is simple and it is known by field experts as ‘predictable ecologies’ (8, 9). In simple terms this is defined by the application of undoubtful standardised methodologies that go from analysing a multicomplex ‘microbiome’ to ultimately relate it to an individualised ecology. Ergo, helping to accurately determine racial traits, geographical origin and other physiological singularities (6), link dynamic bodily fluids (e.g., vaginal, salivary, etc.) to specific individuals (10), generate exclusion hypothesis (11) supported by mathematical algorithms and predictive in silica models that greatly reduce apparent biological confounders (e.g., as with human twins), efficiently identify individual differences based on behavioural aspects and environmental exposure (12), analyse post-mortem, bodily decay and the agonal period (3), predict efficient medical approaches upstream to the infection cascade (13) and so forth.

[1] Aggarwal P, Chopra A, Gupte S, Sandhu S (2011). "Microbial forensics - An upcoming investigative discipline". Journal of Indian Academy of Forensic Medicine; 33.

[2] Fernandez-Rodriguez A, Cohen M, Lucena J, Van de Voorde W, Angelini A, Ziyade N, et al. (2015). "How to optimise the yield of forensic and clinical post-mortem microbiology with an adequate sampling: a proposal for standardisation". European Journal of Clinical Microbiology; 34.

[3] Metcalf J, Carter D, Knight R (2016). "Microbiology of death". Current biology : CB; 26:R561-R563.

[4] Metcalf JL (2019). "Estimating the postmortem interval using microbes: Knowledge gaps and a path to technology adoption". Forensic Science International: Genetics; 38:211-218.

[5] Engstrom-Melnyk J, Rodriguez PL, Peraud O, Hein RC. Chapter 5 - Clinical Applications of Quantitative Real-Time PCR in Virology. In: Sails A, Tang Y-W, editors. Methods in Microbiology. 42: Academic Press; 2015. p. 161-197.

[6] Hampton-Marcell J, Lopez J, Jack G (2017). "The human microbiome: an emerging tool in forensics". Microbial Biotechnology; 10:228-230.

[7] Kuiper I (2016). "Microbial forensics: next-generation sequencing as catalyst". EMBO reports; 17(8):1085-1087.

[8. Riedel S (2014). "The Value of Postmortem Microbiology Cultures". Journal of Clinical Microbiology; 52(4):1028.

9. Gunn A, Pitt S (2012). "Microbes as forensic indicators". Tropical biomedicine; 29:1-20.

10. Leake SL, Pagni M, Falquet L, Taroni F, Greub G (2016). "The salivary microbiome for differentiating individuals: proof of principle". Microbes and Infection; 18(6):399-405.

11. Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R (2009). "Bacterial Community Variation in Human Body Habitats Across Space and Time". Science; 326(5960):1694.

12. Wu H, Zeng B, Li B, Ren B, Zhao J, Li M, et al. (2018). "Research on oral microbiota of monozygotic twins with discordant caries experience - in vitro and in vivo study". Scientific Reports; 8(1):7267.

13. Hemarajata P, Baghdadi JD, Hoffman R, Humphries RM (2016). "<span class="named-content genus-species" id="named-content-1">Burkholderia pseudomallei</span>: Challenges for the Clinical Microbiology Laboratory". Journal of Clinical Microbiology; 54(12):2866.

Post image by Hannah Gibbs on Unsplash

On the management of Paediatric: 1) Vesicoureteral Reflux and 2) Dietary-related eczema

THESE ARTICLES ARE BEING PREPARED FOR YOU AND ARE COMING SOON. STAY TUNED!

Best weaponry for fighting Sjogren's Syndrome - Division Human Shield - Part 3 of 3

Times have been so incredibly busy for me that I looked on the computer clock and said to myself "How on Earth will I find energy to post anything this month"? But I had to find that energy somewhere because the blog must go on, the information is important, the need for information must be satiated and it's all for a greater good. So what do you do on those times when all your energy phased away but you love something so much you need to find the diesel to get yourself going? Having a blog you love is almost like having a child, with the respective emotional integrity but the honesty in the feeling behind loving your blog is vital to maintain it afloat. 

So I just 'scrubbed' my eyes, not rubbed... and decided to play some motivational music that would give the energy but not in a rage type modus operandi. I didn't go for the typical fury-driven songs, I played Jack Johnson and John Legend, dreamt of sharks playing guitars, sea starts dancing on the background and sexy velvety R&B dancers. Crazy stuff? Definitely, but at least I managed to start typing some initial paragraphs towards what is really important, i.e., sharing with you my experiences, my acquired information.

This is the final chapter to the Best Weaponry for Fighting Sjogren's Syndrome - Division Human Shield. The other two parts can be found here and also here. With this third and final part to my personal advice towards a better management of your problem, there is no disregarding of a visit to a specialist. I do it every year by visiting my rheumatologist. And we actually have great conversations. She appreciates my efforts in getting to know this problem better and looking for solutions to remedy it. And I don't say this of medical doctors very often, mostly because some, if not the biggest part of them, are actually arrogant presumptuous people who can't see past their incredibly tough to gain titles. The fact that their jobs exist on the grounds of people being sick and needing treatment says very little to a lot of them. However, I can see a wind of change and some are starting to understand that the very privileged professional group they compose, orbits around the horizon threshold of the black hole that sickness is, especially for something so 'unknown' as Sjogren's Syndrome. Some are starting to understand that humility is the first step towards knowledge, and for one to improve knowledge one needs to admit that there is so much more to learn and a lifetime is not at all enough to know it all.

And because there is no such thing as knowing it all, I decided to share MY learned information, so we can exchange ideas and get much better some day. The recipe is simple, read with interest, judge with impartiality, share with love:

Coconut oil and olive oil instead of hydrogenated fats

(image from bbcgoodfood.com)

Hydrogenated fats/Trans-fats are triggers to inflammation. As simple as it gets. The highest our intake on these type of fats the worse it gets in terms of inflammatory proneness and endothelial function. In addition, a more vegetarian diet, say a much more reduced in saturated and trans-fats and low in protein, is known to result in a profile of higher antioxidant levels, reduced levels of C-reactive protein (an inflammation marker) and lower risk of coronary heart disease [1, 2]. And in all honesty our body does not know very well how to use these hydrogenated/trans-fats anyways, so why poison it any further? If you don't believe me read Kinsella et al (1981) [3]. The good alternative I've been using is coconut oil, the virgin version whenever possible. The anti-inflammatory potential of this natural oil, alongside its anti-pyretic properties has been vastly confirmed with acute inflammatory models [4].

Rice milk instead of cow's milk

(image from superhumancoach.com)

I could come again with coconut milk or some vanilla-flavoured version of soy milk, but let's be creative, original, different. Rice milk tastes awesome, in opposition to almond milk that often makes me wanna puke! Rice milk works in a neutral way on my taste buds and helps me avoid as much as possible dairy. Actually, dairy products are a big NO NO for inflammatory diseases... and also for those who want to have ripe cut bodies for the Summer! The fact that the allergenic/immunogenic potential of dairy can trigger/increase immune/allergic responses is enough information for me. And I tell you of milk as I tell you of honey and peanuts that I also very much reduced to extremely limited consumption. Only when I have stupid cravings I resort to these, but even then I try to have the bare minimum. In addition, I also replaced the typical butter and yogurts for soy butter/yogurts, and/or olive oil butter (it's only 15% olive oil fat in a plant fat emulsion though - but with a really nice taste). 

And this is my final list of tips in regards to dieting. Believe me, after three years these guidelines made a whole lot of difference in my life. Just give it a try yourselves after consulting with a doctor and you might as well enjoy the same benefits I am enjoying these days. Now, in terms of products that help with my eye and mouth dryness, and those that just caused me loads of secondary effects, I have to tell you of the following. I AM NO FAN OF HYDROXYCHLOROQUINE and I definitely do not understand this new wave of applause that looks into this product as if it were the panacea for the immunologic imbalance. Pure stupidity in my humble opinion. A product that takes around 6-month to start producing proper results [5] and in the meanwhile can cause irreparable retinal toxicity with likelihood for irreparable damage [6], can only be a joke. I don't care if they say that the incidence of retinopathy (damage to the retina of the eyes) in users of hydroxychloroquine is low to very low. Vision, and the loss of it, is no joke for one to roulette it.  

Two comfort shields I have been using on a daily basis whenever I am dealing with terrible discomfort caused by Sjogren's on my eyes and mouth are: Hycosan Extra and Boots Expert Dental dry mouth spray. I should be charging these companies for publicity, but believe me these have helped me tremendously along the way. When things get more serious in terms of dry eyes and Hycosan is not enough anymore (which is rare though) I have to resort to a less fluidly and more oily option. This is typical of when I am stuck in closed environments with very active air-conditioning pumps working all day!

     (image from butterflies-eyecare.co.uk)                                                             (image from Amazon UK)

Finally, Naproxen helps when I can't control the inflammation by the rules of diet, but to be fair that happens once every year... which proves my point that this metabolic response can be optimised to reduce our afflictions. 

Remember, no artificial sugars, no 'artificial' fats, no immunogenic foods, no carbonated drinks that will pore your teeth even further. 

Be safe, be well.

[1] Szeto, Y. T., Kwok, T. C., Benxie, I. F. (2004). "Effects of long-term vegetarian dieton biomarkers of antioxidant status and cardiovascular disease risk". Nutrition, 20, pp. 836-866.

[2] Ridker, P. M., Rifai, N. R., Stamper, M. J., Hennekens, C. H. (2000). "Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men". Circulation, 101, pp. 1767-1772. 

[3] Kinsell, J. E., Bruckner, G., Mai, J., Shimp, J. (1981). "Metabolism of trans fatty acids with emphasis on the effects of trans, trans-octadecadienoate on lipid composition, essential fatty acid, and prostaglandins: an overview". American Journal of Clinical Nutrition, 34(10), pp. 2307-2318.

[4] Intahphuak, S., Khonsung, P., Panthong, A. (2010). "Anti-inflammatory , analgesic, and antipyretic activities of virgin coconut oil". Pharmaceutical Biology, 48(2), pp. 151-157.

[5] Hydroxychloroquine, RheumatoidArthritis.net, [https://rheumatoidarthritis.net/treatment/hydroxychloroquine/], last visited on the 11th of June 2017, last update unknown.

[6] Hydroxychloroquin and  Ocular Toxicity - Recommendations on Screening, The Royal Collge of Ophtalmologists - The British Society for Rheumatology, [http://www.bad.org.uk/shared/get-file.ashx?id=774&itemtype=document], last visited on the 11th of June 2017, last updated on October 2009.

Best weaponry for fighting Sjogren's Syndrome - Division Human Shield - Part 2 of 3

Apologies for the time it took me to post the second part of a three-part article on the best weaponry for fighting Sjogren's Syndrome - Division Human Shield. For the first post on the matter please check here.

It has been hectic for me with loads to do at work, the second serious game that I am designing (this time the main topic is forensic science - check here for more info) and also the numerous books that have been piling up on my bed table... because when I manage to go to sleep I'm already a zombie-like creature and very little allows me to remain awaken.

Well, last post on my findings concerning the best natural substances for fighting Sjogren's symtpoms covered the essentials of Turmeric (curcumin), Green Tea (Camellia sinensis L. leaves) and walnuts. Three everyday fundamentals for counteracting inflammation. Today we are going to cover a few more shields with proven sound scientific background information.

Almonds

These nuts are low in saturated fatty acids and rich in saturated fatty acids! At the same time they are rich in dietary phytosterol antioxidants that in animals reduce total serum/plasma cholesterol and low density lipoprotein cholesterol [1] (LDL - commonly known as bad cholesterol because in high levels it is harmful). But the one precious element that almonds contain, and that is primordial for Sjogren's syndrome patients, is vitamin E. That because as you might all know at this point, the dryness peculiar to this syndrome, and that affects among other body parts, especially eyes and mucosal glands, will require vitamin E as a reducer of potential macular degeneration. Because  inflammatory autoimmune diseases have the potential to cause severe and recurrent ocular surface disease, however, the vitamin E present in almonds will require also good levels of vitamin C, beta-carotene and zinc. In addition, vitamin E is also associated to reduced LDL due to its alpha-Tocopherol (1 of 8 isoforms of vitamin E) (also known as the most potent fat-soluble antioxidant in nature) [2]. The fact that vitamin E has been proven (in tested rodents) to protect them against enlargement of lymph nodes and to reduced levels of serum inflammatory factors (e.g., TNF-alpha, IL-6, -10, -12) [3] is also very good news. Remember, Sjogren's patients have ~5% more chances of having a lymphoma.

Blueberries (antioxidants)

(image obtained from organic facts.net)

One great example of the 'quintessential' life style that I have these days is portrayed perfectly by the daily intake of a large bowl of blueberries. I savour it like a wild beast and could live of it for weeks because they have an awesome flavour. Again, another great weapon against macular degeneration and inhibition of inflammation; among figuratively a trillion other benefits (e.g. protecting against cancer, diabetes, memory loss and so on and so forth). The polyphenols present in blueberries, for example the 3-glucoside/arabinoside/galactoside-based polymers, amidst others, once again suppress the pro-inflammatory cytokines IL-1-beta, IL-6 and IL-12 [4]. The benefits are so vast that the only issue I have recognised as negative is glutony, and a mild intestinal disarray because of my inconsolable gluttony. But nothing common sense, that I totally lack when it comes to fruit cravings, can't fix it for you. And to be fair, as a immune system modulator, between taking hydroxychloroquine and eating blueberries everyday, I will always go with the berries, especially because of the severe side effects (strong headaches, extreme sensitivity to light, and above all nausea) felt with the pharmaceutical. How can a product that when taken over long periods can potentially cause irreversible retinal damage be a good option for the public? Mad!

Stevia (instead of sucrose)

(image obtained from www.fitday.com)

People love sugar, and in nowadays's society sugar loves people because it haunts us and daunts us in every little corner shop of this world. But if you have Sjogren's syndrome one of the immediate worries is the progressive, almost galloping tooth decay. Lack of saliva promotes a more acidic environment in one's mouth where enamel will perish and bacteria will thrive, if sugar is readily available. And matter of fact sugar is always readily available in our modern diets, so the idea is to reduce it to the minimum possible. If you want to protect your enamel and assure that you have the least dentin exposed, cut immediately on pretty much all that contains artificial sugars and replace sucrose by this plant-based one. The immediate advantages to using Stevia rather than sucrose are the fact that Stevia is a zero calories product, it's a sugar that isn't metabolised by bacteria that populate the buccal moiety, it won't imbalance the energy levels in our organism, does not contribute to high blood pressure (and I have around 30 to 40% African ancestry so I'm at higher risk), and also extremely important, it won't feed one of the toughest organisms that insist in colonising Sjogren's syndrome's patients - Miss Candida albicans, a God damn persistent organism and tough as hell to get rid of. But believe me, from personal experience, Stevia and dietary discipline really weaken its presence to a minimum and you feel the difference. As reviewed by Thomas and Glade (2010), Stevia is associated to antihyperglycemic, insulinotropic, glucagonostatic, hypotensive, anticariogenic, antiviral, antimicrobial, antiinflammatory, immunostimulatory and chemopreventative effects [5].

I will try my very best to keep responding to all the questions I get, but in the meantime if you do not hear from me, please just browse through the previous posts. Most of the times your enquiry has already been covered in a previous post.

[1] Ling, W. H., Jones, P. J. H. (1995). "A Review of Metabolism, Benefits and Side Effects". Life Sci, 57, pp. 195-206.

[2] Szodoray, P., Horvath, I. F., Papp, G., Barath, S., Gyimesi, E., Csathy, L., Kappelmayer, J., Sipka, S., Duttaroy, A. K., Nakken, B., Zeher, M. (2010). "The immunoregulatory role of vitamins A, D and E in patients with primary Sjogren's syndrome". Reumatology, 49, pp. 211-217.

[3] Venkatraman, J. T., Chu, W. C. (1999). "Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis". J Am Coll Nut, 18, pp. 602-613.

[4] Cheng, A., Yan, H., Han, C., Wang, W., Tian, Y., Chen, X. (2014). "Polyphenols from blueberries modulate inflammation cytokines in LPS-induced RAW264.7 macrophages". International Journal of Biological Macromolecules, 69, pp. 382-387.

[5] Thomas, J. E. and Glade, M. J. (2010). "Stevia: It's not just about calories". The Open Obesity Journal, 2, pp. 101-109.

Best weaponry for fighting Sjogren's Syndrome - Division Human Shield - Part 1 of 3

Sjogren's syndrome is, in simple terms, an autoimmune disease where the person's immune system attacks glands that secrete fluid, be it saliva, tears, etc. Known by many as the sicca syndrome or dry syndrome (since dry eye and mouth are the simplest of the symptoms one can associate to Sjogren's) this syndrome can reveal itself a complicated 'disease' to bear due to its arthritic profile. On the other hand, this syndrome increases in 5% the chances of a person to develop Non-Hodgkin's lymphoma (cancer of the lymphatic system that does not involve the Reed-Sternberg cells).

Among a vast list of complications that can go from glandular manifestations (parotitis, mouth dryness [xerostomia] and eye dryness [xerophtalmya], cornea abrasion, infection or inflammation [keratoconjunctivitis sicca], gum disease, difficulty swallowing, accelerated tooth decay, etc) to extraglandular manifestations (fatigue, tiredness, joint pain, arthritis [joint inflammation], lung inflammation, heartburn, gastroesophageal reflux disease, etc etc etc). The list is extensive even in regards to other associated complications, such as Lupus (also an autoimmune disease where the body attacks different tissue parts of the same) or the Hashimoto's thyroiditis (in which the immune system attacks specifically the thyroid resulting in low levels of thyroid hormones [hypothyroidism]). 

This is a syndrome - some even challenge the definition and actually call it a disease - that usually affects women in between their 40s to 60s. Well, I'm a man, last time I checked, that at the age of 36 was diagnosed with it, but I honestly believe that I've been dealing with it from my early 20s, however the most severe signs started back in 2008.

I 'postulated' (not so arrogantly as the word implies) in this blog several ideas of what I believe is behind the 'uprising' of Sjogren's, to a certain extent, obviously. One of many valid ideas that start emerging since doctor's don't know a lot about the etiology of this syndrome, or even how to cure it, let alone tackle it efficiently (regardless of what they might say this is an irrefutable fact as we speak). Based on an extensive literature review I was able to generate changes in my lifestyle that increased tremendously my quality of life and assured me to counteract efficiently the chronic progression of a health issue that I very much want to erase from my life. Bear in mind that when I looked for help with specialists from the UK and Germany no one offered me a proper diagnosis or even a mild solution. I was the one that in 2015 researched intensively and told the doctor with an open heart and 'humility' in my voice "Doctor, I believe I have Sjogren's". After a sialographic analysis (a radiographic examination of my parotid gland) the typical lesions were confirmed. However, no one told me what to do, what to take, what to think, or even where to go. They just did the best possible to assure that it wasn't progressing to something more serious. This does not intend to say doctors are dumb. This just attests of their limitations as any other human being confronted with the novel, with the unknown.

Like any other autoimmune disease, Sjogren's comes with a panoply of metabolic disorders. Some so immediate and severe that changed my whole life style, and I was already a vegetarian when I was diagnosed. I am taking no pharmaceuticals if not very occasionally when nothing else (not even prevention) works. And this weaponry I am sharing with you today is what in my personal case made the whole difference. It might work for you but not for your neighbor, so don't make it a gospel. However, it is based on scientific facts that I want to share with you.

Welcome to the Dos and Don'ts of my human shield against Sjogren's Syndrome and the reason why this is working 'so well' thus far. Bear in mind that I still think my case is mild as there are people with a lot worse signs and symptoms. Having said that, do not avoid a visit to your doctor before anything else. What might be good for one could very easily trigger something bad in another person:

Turmeric (curcumin)

[Image from Authority Nutrition]

What? The powder of grind Turmeric (Curcuma longa), an anti-inflammatory botanical spice part of the ginger family. 

Why? It addresses the underlying cause of inflammation so much better than them non-steroidal anti-inflammatory drugs that simply counteract the symptom. Contrarily to drugs, curcumin (the active ingredient) have minimal side effects and proven results against leukemia, colon, melanoma and breast cancer cell lines [1]. It triggers mechanisms that produce a decreased expression of pro-inflammatory cell signals (NF-kappaB, prostaglandins, etc) [2].

How? A teaspoon.

When? Every single morning and evening mixed in with my smokin' green tea.

Green Tea 

(Camellia sinensis L. leaves)

[Image from Nutrition-Group]

What? The leaves of the smoke-scented Camellia sinensis L. shrub available at any supermarket these days under the commercial name of 'Green Tea'. 

Why? Its flavonoids content is reportedly associated to antioxidant properties [3], but above all also correlated to anti-inflammatory processes, showing antimicrobial effects (read my posts on the link between H. pylori and Sjogren's to better understand why it's so important), and preventive of tooth decay [4] (anti-xerostomia? Sign me in!!!!). So many ticks in the Sjogren's symptom's list that we should grow the tree ourselves.

How? 3 large warm cups every day.

When? Morning to night.

Walnuts

[Image from Insight Himachal]

What? Walnuts, what else to say. They just taste great!

Why? Because I'm a vegetarian I'm not the richest of the guys in what concerns the fatty acid omega-3 that fishes give you. I have to resort to nuts but don't fool yourself, it is scarce the presence of omega-3 in traditional nuts like almonds, cashews, hazels, pistachios, therefore walnuts gain an enormous relevance. Omega-3 fatty acids need to be consumed within a reasonable ratio to become effective in terms of its anti-inflammatory role and aid against symptoms of dry eye and dry mouth. The omega-3 fatty acids help prevent arthritis and indirectly act in the lacrimal gland to prevent the death of secretory epithelial cells [5]. In addition, the immunomodulatory activity of this polyunsaturated fatty acid is incredibly important for tackling rheumatoid arthritis [6]. 

How? At least 30 g every single day.

When? Any time of the day.

And there is a lot more to tell you, so stay tuned because next posts will bring a lot more DOs and also a lot of NO NOs. As usual, if you'd like to contribute with your personal experience, by all means, just let me know by commenting on this post.

[1] Ramsewak, R. S., DeWitt, D. L., Nair, M. G. (2000). "Citotoxicity, antioxidant and anti-inflammatory activities of Curcumins I-III from Curcuma longa". Phytomedicine, 7(4), pp.303-308.

[2] Daniel, J. W. (2005). "The Sjogren's Book". Oxford University Press. The Sjogren's Syndrome Foundation. 4th Edition.

[3] Sharangi, A. B. (2009). "Medicinal and Therapeutic Potentialities of tea (Camellia sinensis L.) - A review". Food Research International, 42 (5-6), pp. 529-535.

[4] Chattopadhyay, P., Besra, S. E., Gomes, A., Das, M., Sur, P., Mitra, S., Vedasiromoni, J. R. (2004). "Anti-nflammatory activity of tea (Camellia sinensis) root extract". Life Sciences, 74(15), pp. 1839-1849.

[5] Roncone, M., Bartlett, H., Eperjesi, F. (2010). "Essential fatty acids for dry eye: A review". Contact lens and anterior eye, 33(2), pp. 49-54.

[6] Simopoulos, P. A. (2002). "Omega-3 fatty acids in inflammation  and autoimmune diseases". Journal of the American College of Nutrition, 21(6), pp. 495-505.

A comment on 'The New Antibiotic Paradox'

One of my favourite blogs, actually advertised somewhere here in my blog, is called the 'Antibiotics - The Perfect Storm'. They just published a very current and important post on the antibiotic research dilemma and I had to leave them with my opinion. Who do I think I am to just go on leaving my opinion everywhere like that? I'm a guy completely in love with antibiotic research and bacterial toxigenesis. Please find the original post entitled "The New Antibiotic Paradox" HERE, and my opinion transcribed below. Feel free to also discuss the matter hereby if you will.

After a PhD where I was working with synthetic antagonists for Pseudomonas' PqsR, I am inclined to believe that the solution is not entirely about a novel funding strategy. Firstly, the governments must be on the front drive of the train leading by example, doing exactly what the private market is not willing to do. That is why governments exist in the first place (sorry for the obvious exaggeration), but the reality is that a society should always be able to resort to governmental strategies to tackle eminent problems. Waiting for the private market to find a solution for something that is yet a 'somewhat distant' issue will do us no good. Unless nature creates an urgent need for reaction, the private market won't even research a tangible answer for the hypothetical need for antibiotics. The reality is that the media see these new 'iatrogenic superbugs' as something distant and mysterious, when they're just around the corner, waiting for that window of opportunity to really get us with our pants down.

I see the model differently. I see it as a proper research program throughout state universities focusing on a scheme that could be inexpensive and fast. I talk about merging two ideas, 1) the modelling of computerised protein-binding predictions with subsequent testing in live cultures of these developed synthetic molecules, and 2) 'in silico' production of what I'd like to call 'intelligent & versatile' synthetic molecules that with minor changes can rapidly counteract enzymatic inhibition. In what comes to the second point, as far as I could learn from my own research experience and the recent worldwide research on Pseudomonas aeruginosa PqsR antagonists, most of the success comes from using not only halogen particles (F, Cl, Br, I...) and the non-metal sulfur. Additionally, the location of these functional groups, be it on the vicinity of the core structure or along the core structure, is also very important. As it is their distance to the main aromatic clusters!!! The moment we build an intelligent portfolio of easily intra-changeable synthetic antagonists of bacterial virulence pathways, we will open the door to a new world.

Am I right in thinking that? Well, I believe so. But I'd love to hear from experts in this area.

Cheers.

A train of oxidative consequences - manganese and Sjogren's

Here is the follow-up to the post I wrote last time on the tackling of extreme tiredness, a typical symptom felt by Sjogren's syndrome's patients. Remember I did link it to the 'greedy' metabolism of folic acid and vitamin B12 (HERE), triggered by the spiral-shaped bacteria Helicobacter pylori. If you remember there was still a bit of a bridge to build in order to establish a better understanding of the whole chain of consequences. I could not immediately understand how we could go from high homocysteine levels to a manganese deficiency (see diagram on referred post).

OK, but just for the sake of remembering exactly what was mentioned, let me produce a 'train' of consequences hereby:

H. pylori is responsible for the chronic degenerative gastritis -> that results in low plasma levels of folic acid and vitamin B12 -> with produced consequences to our 'chromosomal health' -> responsible for the elevated homocysteine levels (possibly linked to a defective participation of the enzyme methylenetetrahydrofolate reductase responsible for hyperhomocysteneimia) [1] -> resulting in chromosomal imbalance and genotoxicity.

But what is in fact the impact of elevated homocysteine levels in the human blood plasma that is likely to induce a serious reduction in the manganese levels? And what real impact does this manganese deficiency have on patients suffering with Sjogren's syndrome?

Very well! For the bacterium to establish itself in our gastric environment it will have to face a very acidic challenge, i.e., the neutralisation of the gastric juices. And how is this done? By releasing enzymes (arginase and subsequently urease) into the acidic moiety that use up the second-favoured metal co-factor manganese (when cobalt is not readily available) [2]. As simple as that! And that is the primary action that will determine a manganese deficiency in our system. That, alongside the prior folic acid and vitamin B12 reduction (also especially correlated to high homocysteine levels 'in men' as suggested by [3]), complement a very particular and aggressive attack to biochemical 'energy' determinants. Affecting exactly what? The mitochondria and the releasing of reactive oxygen species that will poison our body. Why? Because free radicals will negatively interact in random unexpected ways with numerous other important molecules throughout our organism [4].

With less manganese available the weaponry to detoxify our organism will be found deprived. Because manganese is a component of the superoxide dismutase that acts as a powerful antioxidant. This is why it is so important for those coping with Sjogren's syndrome to have a daily intake of around 30 g of walnuts. Because alongside omega-3 these nuts provide us with important manganese batteries.

There we go! Bridge created. We can now cross to the other side and 'recce'. In the coming Sjogren's syndrome post I will be disclosing my utter secrets on my favourite weaponry against the most limiting symptoms one can be affected with. I will bring a list of the finest guns for your protection and counterattack.

In the meantime and before I go, I must give 'kudos' to an impressive blog that helped me think through the processes when I got stuck in my scientific approach. I read a post that helped me establish this chain of events in a way that I found it so much easy to write after reading it. This is proof that there are very intelligent and dedicated science people writing for the common public these days. The blog I am referring to is called "Gutsy" and you can access it here. Apart from the excessive advertising and the cliché bible verses, said blog is very good indeed.

***

A special thanks to the 'Gutsy' writer of the post:

THE REAL TRUTH ABOUT H. PYLORI: ALLERGIES, AUTOIMMUNE, & ADRENAL FATIGUE

***

[1] Friedman, G., Goldschmidt, N., Friedlander, Y., Ben-Yehuda, A., Selhub, J., Babaey, S., Mendel, M., Kidron, M., Bar-On, H. (1999). "A common mutation A1298C in human methylenetetrahydrofolate reductase gene: Association with plasma total homocysteine and folate concentration". The Journal of Nutrition, 129(9), pp. 1956-1961.

[2] Azizian, H., Bahrami, H., Pasalar, P., Amanlou, M. (2010). "Molecualr modelling of Helicobacter pylori arginase and the inhibitor coordination increases". Journal of Molecular Graphics and Modelling, 28(7), pp. 626-635.

[3] Lussier-Cacan, S., Xhignesse, M., Piolot, A., Selhub, J., Davignon, J., Genest, J. (1996). "Plasma total homocysteine in healthy subjects:sex-specific relation with biological traits". The American Journal of Clinical Nutrition, 64(4), pp. 587-593.

[4] Halliwell, B. (1991). "Reactive oxygen species in living systems: Source, biochemistry, and role in human disease". The American Journal of Medicine, 91(3-3), pp. S14-S22.

Can Folate and Vitamin B-12 be intrinsically related to the onset of Sjogren's Syndrome?

Iatrogenic factors and amphibiotic H. pylori could trigger Sjogren's syndrome. And what else?

It is my personal belief that one of the triggers related to the onset of Sjogren's syndrome symptoms is our so well known bacteria Helicobacter pylori. This alongside iatrogenic factors derived from the use of pharmaceuticals like tricyclic antidepressants or selective serotonin reuptake inhibitors. I am not religiously assuming it, I am conjecturing based on hours of literature research and evidence collected by myself. 

I wrote about the concomitant role of H. pylori in Sjogren's syndrome here, here and also here. In my last post on the subject I stressed the likely amphibiotic behaviour of the bacteria Helicobacter pylori that under attack will determine a shift from the symbiotic to the aggressive-parasitic posture. It is my understanding that whilst under attack the bacteria will make sure the immune system of its host remains busy with capturing decoy substances produced by the invasive agent, to then cause a cascade of actions that ultimately result in the onset of Sjogren's. 

There is a growing wave of acceptance in the scientific community that a viral or bacterial infection can trigger the disease. To that I add that people subjected to, or suffering from severe stress/extreme anxiety are naturally volatile subjects due to a cascade of events that result in stress-induced anxiety and acid reflux. Long story short, stress and anxiety will increase cortisol levels that due to adrenal fatigue and low levels of oestrogen will result in an ever more acid stomach pH. This will reduce mucine levels in our stomach lining, fissures will crack open the surface of an infected digestive wall where the bacteria will start a very resilient amphibiotic process of survival. 

But today, as I was browsing through some articles in the very limited free time I still have, I found yet another incredible piece of evidence for this theory of mine: Folic acid and Vitamin B-12.

Tamura et al (2002) showed that pylori-induced chronic degenerative gastritis reduces both folic acid and vitamin B-12 plasma levels [1] resulting in ailments such as joint inflammation - typical of Sjogren's syndrome. This idea is also vastly and consistently debated by Tollison and Satterthwaite's book "Practical Pain Management" [2]. In addition, if one reads the impressively good review by Fenech (2001) [3] one learns that folic acid deficiency can result in chromosome breaks and hypomethylation of the DNA, both linked to elevated homocysteine levels (also suggested by [1]). High homocysteine levels are linked to chromosomal imbalance and genotoxicity. 

What I am willing to explore over the coming weeks is what some people (I'm not going to say who for I had no time to read their articles yet) are currently suggesting... That all of these events hereby mentioned can 'somehow' result in manganese deficiency. And the lacking of manganese will reveal an incapacity of one's organism to cleanse off free radicals. Those free radicals will allegedly be entrapped at cell membranes and the mitochondrial moiety and be targeted by the body's immune system - A DECOY STRATEGY THAT KEEPS OUR IMMUNE SYSTEM WAY OFF THE REAL ISSUE - H. PYLORI. The body believes that it is making sure the toxic metals are 'exuded', but in reality the attack is constant on the antigen  and never on its precursor - the bacteria. Hidden in the typical muciparous/mucogenic environments, the bacteria thrives on.

That's it for now, folks! Tell me what you think on this matter and come visit the blog next week for the underlying link between the high homocysteine levels and manganese deficiency.

[1] Tamura, A., Fujioka, T., Nasu, M. (2002). "Relation of Helicobacter pylori infection to plasma vitamin B12, folic acid, and homocysteine levels in patients who underwent diagnostic coronary arteriography". The American Journal of Gastroenterology, 97, pp. 861-866.

[2] Tollison, C. D. and Satterthwaite, J, R. (2002). "Practical Pain Management". 3rd Edition, Lippicot Williams and Wilkins.

[3] Fenech, M. (2001). "The role of folic acid and vitamin B-12 in genomic stability of human cells". Micronutrients and Genomic Stability. 

Should we attack our dark angel H. pylori? (The concomitant role of H. pylori in Sjogren's syndrome)

Writing my thesis hasn't been easy when there is so much to do. At home a 2-year old that is a hurricane, running my tiny science serious games business is also mandatory, fulfilling my role as the Midlands Ambassador for PARSUK whilst trying to find a job with the scarce seconds I have left to relax, complicates everything even further. 

This very busy agenda has made me aware of how difficult it is to update the blog, and if I do it it's because of my passion for science communication. I could not leave unfinished my Sjogren's syndrome posts on unveiling the concomitant role of Helicobacter pylori in triggering this autoimmune disease. Especially when yet another friend of mine, a woman this time, came to me saying that she has been recently diagnosed with Sjogren's and she actually had a pylori infection prior to the actual diagnosis.

***

Literature says that a genetically susceptible individual can develop an autoimmune disease such as Sjogren's when the environment conspires to bend and break him. H. pylori being the fierce survivalist we all know remains untouched and no agents can actually get us rid of the bacteria that easy. Tell me about antibiotics, this bug is pretty hardcore hiding and masking its presence. You can very well undergo three courses of broad spectrum antibiotics, most of the times you are just flushing out your commensals and endangering your immune system. And by all means please do not think that because you have an autoimmune disease you have a reinforced immune system working over hours. All you have is a disturbed immune system so rage-drunk a dog it cannot recognise the master hence going bite-happy.

H. pylori is the mail man that really drives our immune system's dog crazy. Hasni et al (2012) talks about findings linking pylori with a deficiency of platelets in the blood [1]. But the most intriguing thing is how does pylori work in repressing our system and surviving such complex and adaptive defenses for longer than 58 000 years ago in human ancestors? Something somehow symbiotic has got to be at stake here, as suggested in [1].

Symbiotic or Amphibiotic?

Could the answer be that whenever we try and treat pylori we switch on a bacterial defense protocol that eventually will lead to unbalanced autoimmune responses? Hasni et al (2012) states that epidemiological data suggest an increase in asthma and autoimmune diseases in populations wherein H. pylori infection is aggressively treated and being eradicated [1].

Point 1: We get to a point where trying to eradicate a bacteria that has been with us for so long and known to cause harm might trigger an immune system imbalance.

Point 2: However, eradication of pylori is not associated to an increase of indigestion in patients with Sjogren's syndrome.

Point 3: Some studies suggest that H. pylori has a protective role in our human biology.

Could it be that we are facing an axiom indicating that H. pylori is likely to be an agent that has a low profile role in our human biology through an amphibiotic relationship (symbiotic or parasitic depending on the context of gastric equilibrium) with us humans?

[2] talks about H. pylori slowly and progressively disappearing from humans' gastric mucosal tissue in the industrialised populations, and with it so are gastric cancer rates falling. What is this dark angel responsible for? Can pylori actually protect us? I don't really think so!

My personal opinion is that as expected H. pylori is terrible for us. But because we are still incapable of getting rid of it that easy it is better to maintain it dormant (reducing stress, changing our diets, etc) and then when really necessary apply a strong, specific and effective pylori treatment. That is in my opinion better than to try and err time and time again with Amoxicillin and Metronidazole that flush away the good guys too. The moment the bacterium recognises it is under attack it will start a process of masking and counterattacking that might as well be responsible for the immune system self/nol-self conflict that characterises Sjogren's syndrome.

Let's explore that in the coming article to be posted as early as January 2016.

[1] Hasni, S. A. (2012. "Role of Helicobacter pylori infection in autoimmune diseases". Curr Opin Rheumatol, 24(4), pp. 429-434.

[2] Blaser, M. J. (???). "Pathogenicity and symbiosis: human gastric colonization by Helicobacter pylori as model system of amphibiosis". nDepartment of medicine and microbiology, NYU School of Mecicine, New York, NY.

Image taken from [2]

The concomitant role of Helicobacter pylori in Sjogren's syndrome (IL-8, TNF-alpha and HCl)

The diagram I wish to build that will ultimately help design a bridge to understanding the concomitant role of H. pylori in Sjogren's syndrome knows today an enhancement. But let me summarise a bit of what was revealed on my last post:

• Chronic gastric inflammation with high prevalence of serum titers of H. pylori causing mucosal atrophy is seen in ~ 80% of patients with Sjogren's syndrome;
• Patients with other connective tissue diseases do not reveal this anti-H. pylori antibodies relationship;
• However, biopsy results do not present an etiological link between H. pylori and Sjogren's patients; nevertheless, there might be genetic/infection differences from country to country;
• Correlation between H. pylori infection of the gastric mucosa and anti-H. pylori IgG serum titers has been revealed;
• Infection by H. pylori and disturbance of immunological mechanisms in Sjogren's syndrome patients may trigger a network of local and systemic reactions.

What else is there available in the literature that can support the concomitant role of H. pylori in the perturbed chain of responses typical of Sjogren's syndrome? 

The quite old discovery by Freimark et al (1989) that shows high serum levels of IL-8 (small signalling protein secreted by epithelial cells, macrophages, smooth muscle cells or even endothelial cells) [1] responding to alterations in the body system. The same pattern is also seen with increased levels of TNF-alpha, another signalling protein present in systemic inflammation and secreted by, for example, activated macrophages [1]. The elevated serum levels of both IL-8 and TNF-alpha reported by Freimark et al (1989) takes place in asymptomatic H. pylori patients who also show signs of increased gastrin (a peptide hormone that stimulates production of HCl in the stomach, duodenum and pancreas. 

As Miedany et al (2005) so well states, this direct relationship can help explain, in the future, if this bacteria is responsible for inducing Sjogren's or maintaining typical Sjogren's responses in the autoimmune scenario of the disease.

On the other hand we have a very interesting link between H. pylori infection and how long the disease actually lasts. The really curious fact is that presented by Fiocca et al (1994) disclosing that H. pylori antigens might be acting as antigen presenting cells recognised by lymphocytes [2]. Hence and in very simple terms, if H. pylori is still present, the organism still maintains an immunological response and the systemic inflammation is pursued. A vicious cycle indeed!

Most importantly, what I take from all this is that eradication of H. pylori might be adequate to alleviate Sjogren's or simply reduce the inflammatory response levels. Especially in avoiding lymphomas [3], a trait somewhat common in Sjogren's patients. 

See you soon in another interesting building of my diagram up there on the concomitant role of H. pylori in sjogren's syndrome. Please contribute with your findings, comments and own experiences.

[1] Freimark, B., Fantozzi, R., Bone, R., Bordin, G., Fox, R. (1989). "Detection of clonally expanded salivary gland lymphocytes in Sjogren's syndrome". Arthritis Rheumatology, 32(7), pp. 859-869.

[2] Fiocca, R., Luinetti, O, Villani, L., Chiaravalli, A., Capella, C., Solcia, E. (1994). "Epithelial cytotoxicity, immune response and inflammatory components of H. pylori gastritis". Scandinavian Journal of Gastroenterology, 205, pp. 11-16.

[3] Nardone, G (2000). "Risk Factor of Cancer Development in Helicobacter pylori". Digestive Liver Diseases, 32(suppl 3), pp. S190-S192.

TODAY IS WORLD SJÖGREN'S DAY!

TODAY IS

WORLD SJÖGREN'S DAY!

World Sjögren's Day commemorates the birthday of Henrik Sjogren, a Swedish opthalmologist who first identified the disease in 1933. Today creates an ideal opportunity for you to talk about Sjogren's with the people in your life and provide much needed awareness for this common yet little known disease. By sharing your story and educating others, you are helping spread the message that Sjögren's is a serious and life-altering disease and it deserves to be recognized. You may also be helping someone who is looking for answers to their problems.

We also encourage you to make a donation today to help further Sjögren's research and awareness. You can donate in honor of Dr. Sjögren, yourself, a loved one. You can also encourage your family and friends to make a donation. Each and every donation will greatly impact the efforts of the SSF.

Thank you for your support. Together we can transform the future of Sjögren's!

The concomitant role of Helicobacter pylori in Sjogren's syndrome - Evidence 1 to 5

                       

Sjogren's syndrome is a chronic inflammatory disorder [1], firstly observed by the Swedish ophthalmologist Henrik Sjogren in 1930. This syndrome is associated with autoimmune disturbance of the exocrine glands [2] by lymphocyte proliferation, mainly resulting in reduced glandular secretions and mucosal dryness, though it can cause a range of other symptoms such as pain and fatigue.

The reasons behind Sjogren's syndrome are still quite unknown and under intense scrutiny. Some clinical scientists relate Sjogren's to hormonal, genetic or environmental factors. However, there is a number of recent articles that support my personal belief that Sjogren's syndrome can result from the activity of the ubiquitous bacteria Helicobacter pylori after events of gastrointestinal stress.

Throughout the coming months I will be doing my own literature research to unveil what of pertinent is known today on the concomitant role of H. pylori in flaring up Sjogren's syndrome. In addition, I will be also looking a little deeper into the fragilities of H. pylori as an organism and presenting you with the latest research breakthrough on antimicrobial agents triggering this gram negative bacteria.

For reasons that have to do with time availability I won't be able to offer all the references consulted, but the most prominent pieces of research. I honestly hope that we can make this ride together and I wish you can contribute with any information you might find pertinent. The link between Sjogren's and H. pylori can be more than a mere coincidence as stated by many authors. 

The information collected from your peers, relatives or observations you have made on your own self (if you suffer of Sjogren's). Even indirect evidences will be taken into account for the building of my diagram/puzzle (see figure above). Evidence by evidence, step-by-step we might build a nice overview that can help us understand the aforementioned underlying role of H. pylori in primary (syndrome developed by itself) and secondary Sjogren's syndrome (in combination with another autoimmune disease) a lot better.

Evidence 1 -  H. pylori is worldwide spread and the commonest bacterial infection colonising the acid secreting part of the stomach where it can live for long periods of time.

Evidence 2 -  H. pylori has been identified as antigenic (stimulating the production of antibodies) for local accumulation of lymphoid tissue.

Evidence 3 -  H. pylori infection triggers either or both local and systemic immune response against bacterial antigens like, for example, the heat shock protein 60 (HSP60).

Evidence 4 - Prevalence of pylori infections and the average quantity of anti-pylori antibodies in sera from patients suffering with Sjogren's were significantly higher [2] than in control groups (even a control group suffering from connective tissue disease).

Evidence 5 - There is a significant correlation between presence of H. pylori Immunoglobulin G and Immunoglobulin M antibodies in patients with Sjogren's.

To be continued...

[1] Sjogren's syndrome, Arhritis Research UK, [http://www.arthritisresearchuk.org/arthritis-information/conditions/sjogrens-syndrome.aspx], last visited on the 20th of July 2015, last update unknown.

[2] Miedany, Y. M., Baddour, M., Ahmed, I., Fahmy, H. (2005). "Sjogren's syndrome: concomitant H. pylori infection  and possible correlation with clinical parameters". Joint Bone Spine, 72(2), pp. 135-141.