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Dermatology Diseasome

Posted on : 06-03-2015 | By : Fabio Sanchez | In : Articles, Uncategorized


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Dermatology Diseasome

Inflammation Mind Map

Posted on : 15-01-2013 | By : Fabio Sanchez | In : Articles, Uncategorized




Inflammation Mind Map


Types of inflammation. Mind Map.

Posted on : 15-01-2013 | By : Fabio Sanchez | In : Articles, Uncategorized


Types of inflammation

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At the heart of psoriasis

Posted on : 06-10-2011 | By : Fabio Sanchez | In : Articles


The insight that psoriasis is more than a skin disorder has been suggested in the international literature since several decades ago. One of the earliest indications that psorias is linked to cardiovascular disease goes back to a report by McDonald CJ and Calabresi P, whom in 1978 published their results on the relationship between psoriasis and occlusive vascular disease (Br J Dermatol 1978; 99: 469–475). Since then, evidence has been accumulating on the relationship between chronic inflammation in psoriasis and increased risk for cardiovascular disease. A huge study from Denmark compared the incidence of atrial fibrillations (heart rhythm disorder) and ischemic stroke (brain damage due to sudden lack of blood supply) between 36 765 patients with mild psoriasis, 2793 with sever psoriasis and 4 478 926 individuals without the disease and found a high risk of such health problems amongst psoriasis patients which seems related to the severity of the disease. This means, the greater the severity the higher the risk. Patients under 50 years of age with severe psoriasis had both higher risk of atrial fibrillation and of ischemich stroke.Details of the investigation can be found here: http://eurheartj.oxfordjournals.org/content/early/2011/08/12/eurheartj.ehr285.abstract


New research finds 30 additional genes contributing to Multiple Sclerosis

Posted on : 12-08-2011 | By : Fabio Sanchez | In : Articles

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A multicenter research coordinated by researchers at Oxford and Cambridge has added 30 more genes to the list of genetic factors involved in the development of Multiple Sclerosis (MS). The list is now close to 50 genes and about 80% of them are linked to immunity. This finding underscores the complexity of this and other inflammatory diseases where every patient is likely to have a unique combination of genetic factors making them susceptible to disease. The hope is that a number of those genes might be relatively more important and that targeting them would be enough to reprogram immunity to keep inflammation away from the central nervous system. Genetic profiling would be a very important tool to detect susceptible individuals, but determining triggering factors from the environment is as important. Other research has shown that smoking is a very important trigger in women with rheumatoid arthritis, making it possible to prevent AR by, among other things, avoiding the habit of smoking. The MS research community is also focusing on finding out if toxins or microorganisms might trigger MS so that preventative measures can be developed; a likely candidate factor is vitamin D deficiency. This recent study will be a pivotal point for functional studies that will describe how those 50 genes cooperate with each other and their environment to allow or prevent MS from emerging.

Link to the study on the genetics of MS: http://www.nature.com/nature/journal/v476/n7359/full/nature10251.html

Treating inflammatory diseases

Posted on : 21-07-2011 | By : Fabio Sanchez | In : Articles

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Being diagnosed with a chronic inflammatory disease brings about the prospect of a long, painful and debilitating experience. Thus, the desire to regain health at all cost becomes a dominant part of the patient’s life. While reasonable, this attitude might under some circumstances blur patient’s judgment, making them vulnerable to abuse. In this article I present my views about certain cognitive biases that might prove costly when taking decisions about treating inflammatory diseases. My motivation is to empower sufferers of inflammatory diseases to take decisions related to their health. Expert opinion is very important, but the patient’s proactive role is also necessary to improve the chances of a proper treatment.

What are cognitive biases? They are faults in the reasoning process brought about by defects in perception or by faulty logic. In other words it is bad thinking that brings us to wrong conclusions because we do not have the necessary and sufficient information or because we interpret information in a prejudiced and faulty way (List of cognitive biases).

For example, if one is upset about being diagnosed with a difficult disease one might be inclined to believe unscrupulous advertising. This contributes to giving certain substances the panacea status or   cure-all. This tendency to focus on stimuli with high emotional content is called attentional bias.

Another common mistake results from the bandwagon effect or the belief that we should do certain things because others are doing it. For example we might believe that if other patients are taking a certain “super” treatment we should do it also, without assessing other relevant information.

We might be presented with a false dichotomy so that one might believe that there are only two ways to treat something but in reality there might be many more options.

Information overload is another phenomenon that can lead us to mistaken thinking. The availability of medical information is a great asset for professionals and patients as well. But too much information can blur our decision making if we focus on the wrong sources. Physicians are realizing that patients come to their practice with a wealth of information about their condition, which can be both useful and dangerous. The danger resides in the fact that there are bits of specialized information that require proper training in order to be interpreted. Patients might develop false expectations or false representations of their disease due to lack of professional training. This situation can even turn patients hostile. Patients might perceive that they are not being taken seriously and turn away from healthcare personnel in search of unorthodox and potentially dangerous alternatives. Knowledge should be interpreted in a contextual manner, every patient lives under particular circumstances that deserve being studied in detail in order to take decisions concerning therapy. A very dangerous way to look for and interpret information is called confirmation bias. In this error of thinking one is inclined to look for information that confirms our own prejudices, disregarding many other sources of information that might oppose our prejudiced views. As dangerous is the framing effect or the tendency we might have to interpret the same information in ways that adapt to different situations. A final bias I want to refer to regarding the search and interpretation of medical information is the neglect of probabilities. Reading a lot of information does not guarantee certainty about how to make a decision. Medical studies are performed so that medical professionals can assess the probability of certain treatment outcomes. If one disregards these studies or lacks the training to interpret them one might reduce the chances to manage the disease in a proper way. Such studies are what differentiate the so called official medicine from unscientific or prescientific medical opinions.

A greater danger however, resides in the fact that the driving force behind production of new therapeutic agents is economic profit. This means that patients and health personnel must hold pharmaceutical industries to high standards. Even though different social systems have organization that surveil drug development and production, there exist also lobbyists that intend to affect political decisions in order to favor the industry. Therefore, it is essential that health professionals as well as patients demand high quality information in order to make decisions. Companies that proactively show accurate and thorough information regarding their products deserve our support. Anyone trying to misrepresent the potential of their products should be met with suspicion. That includes omitting valuable information. A good example of a misinformation campaign aimed at profiteering is what the tobacco industry did to support their economic status. As a patient you deserve to be informed in a responsible manner.

We are entering a promising era in the treatment of inflammatory diseases; scores of molecules are being treated as potential targets for developing new therapeutic agents. But this brings some problems that need to be tackled at the outset. First the desire of material gain is causing that scientists and entrepreneurs alike  race to patent anything that shows some promise. In this feeding frenzy scientific values are often disregarded and exaggerated claims are used as currency to get more funding or claim higher status. This is something that patient organizations and health professionals ought to influence so that scientific rigor will not be compromised. But the greatest challenge, in my opinion,  is that our thinking about treating inflammatory diseases is deeply flawed by our expectations about how a treatment should work vis a vis how it can work in reality under natural constrains. We expect to be cured of our diseases just as many infectious diseases can be cured with antibiotics or as trauma can be repaired with surgery. But regarding inflammatory diseases, the major problem seems to be regulation of complex networks of genes, metabolites, cells and tissues. Thus for example, anti-TNF biologicals cannot be considered a cure. Biologicals that reduce the bioavailable levels of TNF in the body are a great promise for treating inflammatory diseases but we are far from understanding all their potential and limitations because research seldom focuses on how anti-TNF affects can be called the “TNF network”. TNF is but a node in that network, the other connectors in the network might be crucial for controlling other functions in the body thus making it possible that, if one blocks TNF without understanding the entire network, undesired effects will emerge. There are already many articles that describe problems that arise from treating patients with the accepted anti-TNF biologicals (infliximab, etanercept & adalimumab), you can visit the National Center for Biotechnology Information of the US if you want a list of such articles.

Next generation biologicals will probably be developed in such a way that we will know how much anti-TNF or how much antagonist for other cytokines must be given. We will also know which and how other parts of the cytokine network will be affected  after giving different amounts of the biologicals.  Because every individual has a particular combination of genetic variations that might influence how different metabolic networks work, it will be possible also to determine how different combinations of genetic variants should be treated. Until then we can only strive to communicate with politicians and researchers as well, demanding that the scientific integrity of this type of research is guaranteed. Also, through patient organizations, patients can support the companies and researchers that best represent their interests.

The inflammation Diseasome

Posted on : 07-07-2011 | By : Fabio Sanchez | In : Articles


Inflammation Diseasome

Inflammation Diseasome: This network illustrates the complexity of the genetics involved in inflammatory diseases. Every disease here is represented as a square with colors ranging from white to red. The size of the squares indicates the number of connections drawn from the corresponding node. Every disease has several genes associated with it and in some cases diseases are connected to each other through one or more genes. Every line is labelled with the chromosomal region where the genes are located. The thickness of the lines indicates the frequency with which a genomic region is associated with some of these inflammatory diseases. Feel free to rearrange this network as you study this aspect of inflammation. This network is an attempt from the author to represent common genetic factors in inflammation from a global perspective, following the concept of diseasome as developed by Albert-László Barabási and collaborators. 

Thanks to Christian Tannus Lopes & Max Franz for insights into  embedding networks using Cytoscape Web. / Fabio Sánchez
Cytoscape Web will replace the contents of this div with your graph.

Autoimmunity & protein modification

Posted on : 26-06-2011 | By : Fabio Sanchez | In : Articles

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Our experience of the world is possible because of innumerable bits of information speeding through our senses but at a more essential level our very being is possible because of innumerable messages coded in our DNA and in our environments. Our genes code for precise messages, that reach their destination after being modified by different metabolic processes. The central theorem of genetics says that DNA contains the code necessary to produce all the proteins in an organism. Those coded messages, that we call genes, get transcribed into RNA and after translated into proteins by specialized molecular machines. This view is accurate but not quite complete. Proteins in their final forms are not exact reflections of their original DNA code. During their production they suffer modifications that are not coded into their original DNA, although some sequences -hidden messages – inside the proteins influence how their own chemical modifications are carried out by other molecules we call enzymes. Thus, the original appearance of a protein after being produced is short lived. Protein surfaces get folded onto each other giving each protein a characteristic three dimensional appearance. After, proteins often get linked to other proteins or to other types of chemicals that modify protein structure and function. For example sugars are added in a process called glycosylation,  methyl groups are added in a process called methylation and so on and so forth. thus, methylation of histones, the proteins that help DNA maintain their structure inside cells, is responsible for silencing certain genes during embryonic development. Likewise, addition of diverse types of sugars or other chemical groups to proteins is very important for the proper functioning of our bodies. But sometimes, such chemical changes on our proteins, occur because of foreign substances that enter our bodies, for example, infections or chemical pollutants. One such situation seems to happen in some patients with rheumatoid arthritis (RA) who have the habit of smoking. It appears that people with certain genetic predisposition change the appearance of their normal cartilage proteins through smoking. Their own immune systems stop recognizing such proteins as part of the body which causes an autoimmune reaction, or self inflicted damage. The chemical change is called citrullination and the self inflicted damage becomes what we know as rheumatoid arthritis. Citrullination is not the only change that happens in RA but it is an important contributing factor.
It is possible that specific autoimmune diseases have each specific chemical changes to specific types of proteins, which could explain why chronic inflammatory diseases have different clinical manifestations.
It is therefore important to recognize the people who are likely to respond in such a negative way to smoking and possibly other forms of chemical pollution by studying their genetic profiles. Citrullination in relation to RA is discussed in detail in the following link:
Semin Immunol. 2011 Apr;23(2):92-8. Epub 2011 Mar 3.

Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis.

Inflammation begins with a trigger

Posted on : 11-06-2011 | By : Fabio Sanchez | In : Articles

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Our bodies are programmed to save heat when exposed to cold environments and to lose heat in warm environments. When we are cold, our peripheral circulation slows down, our muscles contract and shake and our movements become sluggish. In warm places we release heat through the widening of blood vessels and sweating. Our neuro-hormonal thermostat regulates all body systems in order to maintain the right temperature, which translates into metabolic balance inside our bodies. Similar systems function in an autonomous manner to keep our energy supply, to contain or control injuries after trauma, to promote reproductive behavior, etc. Metabolic programs, reflexes and instinctive behavior help us maintain our basic functions in balance, they are essential tools that allow us to adapt to our environment. Inflammation is an essential mechanism whose primary function is to contain and repair any damage to our organs. In reality it is not possible to think about inflammation as an isolated mechanism. Whenever it becomes activated, all other systems in the body are affected.  Inflammation results from the crosstalk between many different bodily functions in response to some external challenge. Scientists are finding evidence that certain groups of molecules initiate and propagate the inflammatory responses.They have been named inflammasomes.   What are inflammasomes? why are they relevant to inflammatory diseases? Do they really exist or are they constructs of our imagination?

Articles about inflammation and inflammatory diseases

Posted on : 11-06-2011 | By : Fabio Sanchez | In : Articles