Genetic Variation In The Maintenance of HIV Seronegative Status Among High-Risk Populations

Chemokine receptors have proved to be important in maintaining seronegative status among individuals who have a high risk for contracting the HIV virus. Cultures of lymphocytes and macrophages have shown that those who are relatively resistant to HIV infection secrete high levels of co-receptors CCL3, CCL4, and CCL5 when they are inoculated with this virus. It has been discovered that HIV resistant people are homozygous for an allelic, nonfunctional version of the CCR5 co-receptor, D32. In the Caucasian population, the prevalence of this frameshift mutation (coupled with a protein truncation) in the homozygous form is fairly high at about 1%. The heterozygous allelic form of this mutation may provide some modest protection against the sexual transmission of the HIV virus, and could even slow the progression of existing infections. In addition to this, variation in the promoter region of the CCR5 gene has been identified in both Caucasians and African Americans. Differences in promoter regions have also been associated with different rates of progression of the disease. This evidence shows that CCR5 is the major macrophage and T-lymphocyte co-receptor used by HIV to establish initial infection. Interestingly, this also offers hope that primary HIV infection can be blocked by anti-CCR5 receptors.

Janeway, Charles. Janeway's Immunology - 7th Edition / Kenneth Murphy, Paul Travers, Mark Walport. Garland Science. 2008.

Worm therapy available--legally?

Scraping my net over the bottom of the Web, I found Ovamed GmbH, a company in a village near Hamburg that claims to be licensed by the Thai Ministry of Health to sell TSO (Trichuris suis ova) for treatment of Crohn's and UC in those "with a medical recommendation."

And another outfit, Autoimmune Therapies, will sell you a similar product. Here's what they say: "Helminthic therapy, nature's most powerful probiotic, harnesses nature to heal, restoring the helper organisms we co-evolved with and that our immune systems depend on to function correctly, and is based on sound science. Stop treating the symptoms, fix the problem." You can judge for yourselves the accuracy of those statements. They say they sell anywhere except the USA.

There are many more, springing up all over the world, wherever evidence-based medicine is not currently the fashion.

Aquagenic Urticaria (Physical Urticarias)

Physical urticaria refers to a class of chronic urticaria, a hive or wheel type reaction, to a physical stimulus. The literature seems to indicate that for some patients the specific physical trigger results in hives, but in others the stimulus is the only common factor in the otherwise idiopathic condition. A large group of physical stimuli have been characterised and used as diagnostic criteria (1), which include: dermographism, delayed pressure urticarias/ angioedema, cholinergic urticaria, local heat induced urticaria, exercise induced urticaria, solar urticaria, vibrational angioedema, and aquagenic urticaria.

Though fewer than 50 cases of aquagenic urticaria have been documented in medical journals, relatively recent online tabloids and blogs have written articles about the condition (2,3). The clinical features of the condition include small perifollicular wheels on any skin region after contact with water (distilled, tap, or saline). For some patients characteristics of the water effected the condition, salinity, pH, and others factors (4,5). Many patients suffering from aquagenic urticaria have also been diagnosed with cholinergic urticaria or dermographism (6,7).

From the known mechanism of the immune system we have learned about this year it seems unlikely that water itself could be recognized by the immune system. However, a few hypothesis for the mechanism of the condition have been proposed. It is possible that the water acts to carry an antigen (possibly sebum) through from the epidermis to the dermis where it is recognized by mast cells causing the localized reaction (8). Further studies with this hypothesis demonstrated that organic solvents increased sensitivity to the reaction, and removal of the stratum corneum layer of the skin produced similar results. Another theory suggested cholinergic activation resulted in the reaction, scopolamine was shown to decrease reactions in two patients, but pre-treatment with atropine did not suppress reactions. The injection of methacholine, which usually elucidates cholinergic reactions for diagnostics was negative when tested on aquagenic urticaria patients (9). It may also be possible that the activation or involvement of the sensory neurons, perhaps presenting antigens from a latent virus could provide a possible mechanism, though no research has been done in this vein. Similarly, it is possible that ions in the water change an already present molecule of self into a recognizable antigen.

Elucidating a mechanism, or further understanding of aquagenic urticaria and other types of physical urticaria may provide immunologists new insights into antigen presentation, and inflammation.


1. Kontou-Fili, K, Borici-Mazi, R, Kapp, A, et al. Physical urticaria: classification and diagnostic guidelines. An EAACI position paper. Allergy 1997; 52:504.
2. http://www.dailymail.co.uk/news/article-520329/The-teenage-girl-allergic-WATER.html
3. http://abcnews.go.com/Health/AllergiesNews/story?id=7401149&page=2
4. Gallo, R, Cacciapuoti, M, Cozzani, E, Guarrera, M. Localized aquagenic urticaria dependent on saline concentration. Contact Dermatitis 2001; 44:110
5. Tkach, JR. Aquagenic urticaria. Cutis 1981; 28:454
6. Parker RK, Crowe MJ, Guin JD. Aquagenic urticaria. Cutis. 1992 Oct;50(4):283-4
7. Luong KV; Nguyen LT. Aquagenic urticaria: report of a case and review of the literature. Ann Allergy Asthma Immunol. 1998 Jun;80(6):483-5.
8. SHELLEY, WB, RAWNSLEY, HM. AQUAGENIC URTICARIA. CONTACT SENSITIVITY REACTION TO WATER. JAMA 1964; 189:895
9. utdol.com

CRP and COPD

I found this article to be very interesting as I currently work in research looking at the association between COPD (chronic obstructive pulmonary disease) and CVD (cardiovascular disease). I found this article in the European Journal of Internal Medicine 19 (2008) 104–108.
Authors: Fisun Karadag, Sevin Kirdar, Aslihan B. Karul, Emel Ceylan

Title: The value of C-reactive protein as a marker of systemic inflammation in stable chronic obstructive pulmonary disease


In this article the authors sought to evaluate circulating CRP levels in order to determine the value of CRPas a biomarker of systemic inflammation and as an indicator of malnutrition or severity of COPD in stable COPD patients in comparison to the proinflammatory cytokines TNF-α and IL-6.

The study consisted of 35 male patients with stable COPD and 30 age and sex matched controls with normal pulmonary function. Serum CRP, TNF-α, IL-6. levels were taken from the subjects. It was found that CRP levels were significantly higher in stable COPD subjects than in control subjects however, TNF-α and IL-6 were not significantly different. When BMI was taken into account then it was found that COPD subjects with low BMI had a higher serum CRP and TNF-α levels compared to COPD subjects with normal to high BMI.

The authors came to the conclusion that the present study confirms that because circulating CRP levels are higher in stable COPD patients this may be regarded as a valid biomarker of low-grade systemic inflammation. Also, because CRP and TNF-α were higher in the COPD patients with a low BMI then this could be considered an indicator of malnutrition in COPD patients.
The results of this study could be applied to the current study in which I am working looking at COPD and CVD. Using CRP as an indicator of low grade systemic inflammation could be utilized when we are looking at the occurrence of coronary calcium development in those with varying severity of COPD and outcomes such as stroke or heart attacks. Based on these results, I would expect those with lower COPD severity (goldstage 1) to still be at increased risk for heart attacks and stroke. This would be contradictory to the current notion that goldstage 1’s are not really COPD thus the lack of contribution to cardiovascular disease. The other results identifying higher CRP and TNF-α indicating malnutrition could e applicable to studies looking at muscle/tissue wasting in COPD subjects.

Food allergies--peanut/tree nut

Being one of the clinicians in this course, I thought I would share some information about food allergy (which is an issue we encounter with increasing frequency):

Food allergies are adverse immunologic reactions to food proteins and run the spectrum of IgE mediated reactions to cell mediated reactions such as food protein induced enterocolitis or contact dermatitis. However, IgE mediated food reactions are the most common.

Food allergies are prevalent with reproducible symptoms in 5% of young children and 1-2% of adults. More than 90% of food allergies are caused by milk, egg, fish/shellfish, wheat, soy, peanut/tree nuts. It is estimated that 1-2% of the U.S. and European population is allergic to peanuts and/or tree nuts.

Furthermore, reactions to nuts, particularly peanut are severe and often fatal. In fact, per the United States Food Allergy & Anaphylaxis Network (FAAN) registry, peanuts are responsible for a significant percentage of food-associated deaths. Unfortunately, accidental exposure to peanuts is common, noted to occur in 14.3% of Montreal schoolchildren, and exposure to doses as small as 100 micrograms may provoke symptoms (an average peanut weighs 300-500 milligrams). Approximately 20% of children will outgrow a peanut allergy (approximately 10% outgrow tree nut allergy).

Interestingly, nearly one-third of peanut allergic patients will become tree nut allergic and this trend seems to be true of tree nut allergic patients becoming peanut allergic, at least for some tree nuts, such as cashew. So, is it that nut allergic persons are predisposed to develop allergies to multiple different nut proteins? Or are they reacting to similar epitopes in the various types of nuts? The answer is unclear for several reasons. First, and most obviously, not enough work has been done between peanut and tree nut cross reactivity. Second, how do we assess cross-reactivity? Do we use methods that denature the protein and exposure linear, but not necessarily functional epitopes, such as Western blotting? Or do we use functional assays that use structurally intact proteins such as histamine release assays (human basophils or immortalized rat basophils)? Also, how do these studies correlate with the clinical history as well as measurements of peanut or tree nut specific IgE? This is the subject of some ongoing research being conducted here as well as a few other sites in the U.S. and Europe, and perhaps elsewhere.

As a final note, there are a few articles that demonstrate transfer of allergies in the context of transplantation. The first article by Bellou et al. involves bone marrow transplantion. The second article by Phan et al. involves liver transplantation. The third article, which did not have an abstract available online reports peanut hypersensitivity transfer via fresh frozen plasma. The mechanism responsible for the transfer of allergy is undetermined but ideas include adoptive transfer of primed donor B-cells or T-cells, or the transfer of donor mast cells sensitized to peanut specific-IgE or passive transfer of donor peanut specific-IgE.

Articles:

Bellou A, et al. Tranfer of atopy following bone marrow transplantation. Ann Allergy Asthma Immunol. 1997 May;78(5):513-6.

Phan TG, et al. Passive transfer of nut allergy after liver transplantation. Arch Intern Med. 2003 Jan 27;163(2):237-9.

Arnold DM, et al. Passive transfer of peanut hypersensitivity by fresh frozen plasma. Arch Intern Med. 2007 Apr 23;167(8):853-4.

References:

Sampson H. Update on food allergy. J Allergy Clin Immunol 2004;113:805-9.

Bock S. Prospective appraisal of complaints of adverse reactions to foods in children during the first three years of life. Pediatrics 1987;79:683-8.

Hefle S, Nordlee J, Taylor S. Allergenic Foods. Crit Rev Food Sci Nutr 1996; 36:S69–S89.

Sicherer S, Furlong T, et al. A voluntary registry for peanut and tree nut allergy: Characteristics of the first 5149 registrants. J Allergy Clin Immunol 2001;108:128-32.

Sicherer S, Sampson H. Peanut allergy: Emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol 2007;120:491-503.

Yu JW, Kagan R, Verreault N, Nicolas N, Joseph L, St Pierre Y, et al. Accidental ingestions in children with peanut allergy. J Allergy Clin Immunol 2006;118:466-72.

Roux K, Teuber S, et al. Tree nut allergens. Int Arch Allergy Immunol 2003;131:234-44.

Fleischer D, Conover-Walker M, et al. The natural history of tree nut allergy. J Allergy Clin Immunol 2005;116:1087-93.

Burks K, Bock S. Natural History of Peanut and Tree Nut Allergy: Development of Tree Nut Allergy/Sensitization. J Allergy Clin Immunol 2008;121:S235.

Nicotine, Anti-Inflammatory H1N1 Cure

With the recent global outbreak of H1N1, there have been many theories for different vaccines to cure H1N1. Lucky for us some of those theories have been approved by medical researchers and the FDA and vaccines have been produced to cure the people who are affected with the disease. Ironically, there is another theory that you all may find controversial, which I find interesting to blog about and read your comments.

Doing some research on Anti-Inflammatory drugs/remedies using the world wide web, I came across this article stating that Nicotine from tobacco has an anti-inflammatory affect via the vagus nerve which can block a variety of cytokines of the H1N1 virus. Last week in discussion, we talked about the "risk/benefit" theory, where taking an Anti-Inflammatory drug can initially be beneficial, but if that drug is overused, the risk is damage to the GI tract, liver, and can raise blood pressure.

In regards to this article, the "risk/benefit" theory can be applied as well. The article does mentioned that smoking is very toxic to the body, but the nicotine in tobacco can act as an anti-inflammatory and as long as nicotine is present in tobacco, the degenerative effects from inflammatory diseases will be moderately controlled.

Nicotine stimulates the cholinergic anti-inflammatory pathway. At the end of this pathway are immune cells that produce anti-inflammatory cytokines that block inflammation. Thus, nicotine, although one of the most addictive chemicals, can have beneficial effects on inflammatory diseases, such as arthritis, asthma, cancer, inflammatory bowel diseases and perhaps, H1N1.

Tobacco Smoke Is Toxic but also Anti-Inflammatory
Paradoxically tobacco smoke contains hundreds of toxic and carcinogenic chemicals that produce inflammatory reactions and numerous degenerative diseases, but it also contains nicotine that is anti-inflammatory. Smokers assault their bodies, but moderate and obscure the inflammatory degeneration and disease, until they stop the nicotine exposure.

Nicotine Withdrawal Is Inflammatory
The anti-inflammatory benefits of nicotine reveal the inflammatory basis of many unexpected diseases. Nicotine withdrawal is severe, partly because it leads to rebound release of inflammatory cytokines, inflammation and inflammatory disease symptoms that include depression and obesity. Smoking cessation may contribute to more severe symptoms of H1N1 infections.

Nicotine Acts via the Vagus Nerve
Attempts to augment bypass surgery for weight reduction have encountered the anti-inflammatory benefits of stimulating the vagus nerve. Vagus nerve stimulation via an electrode attached to the left branch in the neck by a device implanted behind the clavicle, reduces inflammatory cytokine production and is an effective treatment for obesity. Other types of vagus stimulation are being tested for efficacy in treatment of numerous inflammatory diseases, including arthritis, allergy, asthma, Alzheimer’s, etc.

Nicotine Blocks Cytokine Storms
Cytokine storms are a deadly consequence of inflammation that is out of control. These exaggerated host responses are targets for bioterrorism, because it takes very little toxin or a very minimal infection to be lethal, if it produces a cytokine storm. In mice, the ricin toxin, a bioterrorism agent, induces a cytokine storm that kills by multiple organ failure. Ricin-treated mice can be protected by nicotine prior or after the cytokine storm begins.Read more: http://diseases-viruses.suite101.com/article.cfm/nicotine_antiinflammatory_h1n1_cure#ixzz0YMYaYMWp

In my opinion from a person who does not smoke, I think when it comes to using tobacco whether it be from cigarettes or chewing to receive a source of nicotine to fight inflammation, the risks of smoking to receive a source of nicotine out weigh the benefits. Smoking can cause lung cancer, throat cancer, severely raise a person's blood pressure, effect a person's physical appearance, and can become addicting to where a person can't go through a day without having a smoke. There are other ways to fight inflammation that are less harmful to a person than using nicotine and I believe a person who smokes to fight inflammation should reconsider and look at other healthier treatments like changing their diet, exercising, etc.

Mabley JG, Pacher P, Szabo C. Activation of the cholinergic anti-inflammatory pathway reduces ricin-induced mortality and organ failure in mice. Mol Med. 2009 Feb 11. [Epub ahead of print]
Gwilt CR, Donnelly LE, Rogers DF. The non-neuronal cholinergic system in the airways: an unappreciated regulatory role in pulmonary inflammation? Pharmacol Ther. 2007 Aug;115(2):208-22.
Johnston GR, Webster NR. Cytokines and the immunomodulatory function of the vagus nerve. Br J Anaesth. 2009 Apr;102(4):453-62.Read more: http://diseases-viruses.suite101.com/article.cfm/nicotine_antiinflammatory_h1n1_cure#ixzz0YMchF3PY

Electro-acupuncture

In our acupuncture discussion last week, I had briefly mentioned about “electroacupuncture”. It was my first time hearing this term so I looked up for more detailed information on this subject…if anyone’s interested in it as well!

We all have a general idea of how traditional acupuncture works…
Electroacupuncture stem from the same idea of using needles on the acupoints but with the needles attached to a device that generates continuous electric stimulation. Another term for electroacupunture is “Percutaneous Electrical Nerve Stimulations (PENS)”

There are three main benefits of using electroacupunture:
1. It substitutes for prolonged hand manoeuvring. It helps to assure that the patient gets the amount of stimulation needed in case of the acupunturist’s pause due to fatigue. It also helps to reduce the total treatment time by providing continuous stimulus as well as the chances for the acupuncturist to attend other patients.
2. It can provide a stronger stimulation without causing tissue damage. Strong stimulation may be necessary in difficult cases such as neuralgia or paralysis.
3. Electroacupunture makes it easier to control the frequency and the amount of stimulus in comparison with hand manipulation of the needles.

There is one disadvantage of electroacupunture --- the lack of direct acupuncturist participation. It limits the opportunity for the acpunturist to respond to changes that are taking place during treatment.
According to the Chinese literature, good results are expected from electroacupunture especially in treatment of neurological diseases, including chronic pain, spasm, and paralysis. However, the method should be used with caution in patients with serious cardiac disease. It’s generally recommended to avoid placing electrodes near the heart to prevent the adverse responses of the heart to electrical impulses. In addition, the path between any two electrodes should not cross the heart area as well. Some have also suggested avoiding placing electrodes to needles on both sides of the spinal cord no matter how low the current that’s being used, because of the possible effect of the electrical stimulus on the nervous system.

Similar to the traditional acupuncture treatments, the electroacupunture treatment experiments also revealed conflicting outcomes. The majority of journal articles from China on electroacupunture are devoted to laboratory animal studies. Those studies have limited relevance to humans due to the difficulties matching points on these animals with those on humans. Therefore, electroacupunture animal studies mainly provide a means of using an animal model to study acupuncture therapy in general.

This following short video provides the basic idea as well as demonstratio of both traditional and electroacupuncture!



Here is the link if the short video does not show on your computer.
http://www.youtube.com/watch?v=bvlxggeIG4E&feature=related





References

http://www.itmonline.org/arts/electro.htm Electro-acupuncture Subhuti Dharmananda, Ph.D, Director, Institute for Tranditional Medicine, Portland, Oregon
http://en.wikipedia.org/wiki/Electroacupuncture Electro acupuncture
http://www.youtube.com/watch?v=bvlxggeIG4E&feature=related Acupuncture treatment - the basics. Tom Kennedy