Can Bees Stop Disease?

Last week in PSIO 495K our class discussed how inflammation can affect arthritis. In the review article entitled, "Cytokines in the pathogenesis of rheumatoid arthritis," one of the inflammatory cytokines that was discussed was Interleukin-17. IL-17 is a potent inflammatory cytokine which is secreted by T-helper 17(Th-17) cells. In the above mentioned article by McInnes et al, they concluded that these Th-17 cells are "the key effector-cell subset in inflammatory arthritis." This statement must be qualified with the fact that this inflammatory research was done in rodents and therefore cannot always be transposed to the human immune system. The review article was able to show however that inhibition and stimulation of Th17 had a much greater impact on collagen induced arthritis when compared to the other inflammatory Th1 classes of T cells. Specifically Th17 stimulates chondrocyte mediated matrix degradation in cartilage, increases RANKL mediated osteoclastogenesis, increases the invasion rate of synovial fibroblasts and finally it increases inflammatory cytokine production. At the end of this review article it stated that treatment of rheumatoid arthritis is limited to TNF-alpha antibody therapy.

A more recent research article¹ shows that a resinous substance collected by bees can have immunomodulatory effects. Their research group showed that this resin called propolis can reduce the disease severity of collagen-induced arthritis in rats. The disease amelioration mechanism is due to the effect propolis has on the production of interleukin-17. This research group found that not only does propolis inhibit the secretion of IL-17, the resin also inhibits the differentiation of inflammatory Th17 altogether. Surprisingly this article did not elaborate about the proposed clinical benefits of using propolis as a treatment for RA.

A separate article written by Lupperts et al² demonstrated how their anti-IL-17 antibody could in fact be used therapeutically to reduce the severity of arthritis. They were eager to point out that their anti-IL-17 therapy positively affects both early and late stage arthritis. Experimentally this was shown in mice models which upon exposure to anti IL-17 antibodies had less proteoglycan depletion, less synovial inflammation, less cartilage erosion, less bone erosion and less chondrocyte death.

Perhaps in the future the natural propolis remedy will be able to be used therapeutically. This could be a region of research where physicians, scientific researchers and natural health fields could all work together. This is because these studies have shown that propolis and other suppressers of IL-17 and Th-17 have beneficial effects on arthritis. It would be interesting to see the effectiveness of this remedy in humans as opposed to rats and whether this immune system suppressor might have other systemic impacts. The effectiveness of this therapeutic resin would depend on whether these systemic impacts were mostly positive or negative.

1. Suppression of interleukin 17 production by Brazilian propolis in mice with collagen-induced arthritis. Tanaka et al.


2. Treatment With a Neutralizing Anti-Murine Interleukin-17 Antibody After the Onset of Collagen-Induced Arthritis Reduces Joint Inflammation, Cartilage Destruction, and Bone Erosion. Lubberts et al.

Fact or Fiction: Cracking knuckles causes arthritis....

"Don't crack your knuckles! You're going to get arthritis when you get older!" was something I got told often as a kid. I kept doing it anyway. After learning that osteoarthritis is the 'wear and tear' type of arthritis, I began to believe this myth. I decided to look this up further than just asking and was somewhat surprised to what I learned. I researched and found an article regarding a study correlating knuckle cracking to hand detrimental (like osteoarthritis) and in fact there is no correlation between the two. This study describes what happens when you crack your knuckles. There is actually no 'wear and tear' on the cartilage. What does happen is a release from gases in the synovial fluid after the tension from cracking the knuckle changes the pressure in the cavity. There is a decrease in grip strength and ligaments may be injured; but the most important thing is: it does not cause osteoarthritis!

http://osteoarthritis.about.com/gi/o.htm?zi=1/XJ&zTi=1&sdn=osteoarthritis&cdn=health&tm=85&f=00&tt=12&bt=0&bts=0&zu=http%3A//www.pubmedcentral.nih.gov/articlerender.fcgi%3Fartid%3D1004074

Click here to go to the article.

Revaccination of HIV infected children

Immunologic Basis for Revaccination of HIV-infected Children Receiving HAART
This article is an interesting discussion of potential public health surrounding HIV positive children and immunizations. Untreated HIV reduces the ability of a child’s immune system to respond to infections and vaccines. As the mortality rate decreases, there is a growing need to understand how HAART affects immunity to vaccine preventable infections, with the goal to improve individual and public health. Studies have demonstrated that immune reconstitution following HAART mirrors that of the immune system over the individual life span. Young children with few memory cells will reconstitute with naïve T cells. Adolescents or young adults will reconstitute with a combination of naïve T cells and memory T cell expansion. Older adults will reconstitute with the expansion of memory T cells. When a child is infected perinatally it is believed this predisposes the immune system towards effector T cells.
The authors use the measles virus as a model to study immunological memory. Exposure to measles generally results in lifelong protective IgG antibody levels. When a child is HIV infected there are typically low levels of immunity seen in response to vaccines given prior to initiation of HAART. Studies with Zambian and Thai children have shown a decrease in immunity levels over time, producing a group of measles susceptible children. Determination of the optimal time to revaccinate HIV positive children is not yet clear but emerging data suggests that children who respond to HAART may successfully be revaccinated when CD4 cells return to normal levels for age.
Rainwater-Lovett, K. & Moss, W. J. (2011). Immunologic basis for revaccination of HIV-infected Children receiving HAART. Future Virology, 6(1), 59-71.

Do spices such as curcumin and turmeric have clinical uses?

Earlier this year in the University of Arizona's inflammation colloquium we discussed the affects of curcumin on obesity, diabetes and inflammation. Weisberg et al¹ concluded that dietary curcumin would positively affect insulin tolerance in mice and thus positively affect diabetes in rats. Mice that were fed curcumin also gained weight despite actually eating more food than the control mice. Curcumin infused diets were also found to increase the presence of adiponectin an anti-inflammatory cytokine. Finally curcumin diets lead to an overall decrease in liver weight, liver steatosis and a decrease in inflammatory hepatic cytokines.

The abstract of this curcumin article seems to indicate that curcumin can be used to treat a variety of diseases related to metabolic syndrome in mouse models. However upon further reading and discussion, our class determined that dosage of curcumin that was administered to these mice was unreasonably high. Therefore it is difficult to extrapolate the results of this study to the human metabolic syndrome.

Recently a lay article was published in the Arizona Daily Star which addressed the turmeric based research of Dr. Janet Funk and Dr. Leslie Ritter at the University of Arizona. This article opens by saying that there are no “preventive treatments for stroke” but that turmeric could “help prevent the third leading cause of death in the United States, stroke.” There are some problems in this lay article. The newspaper article makes a list of untenable arguments based on Turmeric “clinical trials.” These trials are not in fact clinical because they were done on rats. The claims in this article regarding the effectiveness of turmeric are based on these professor’s unpublished results which seems to be a premature way of writing a story. To the author’s credit he did not use any language which explicitly said that turmeric prevents stroke.

The author at the Arizona Daily Star allowed Dr. Funk to describe reperfusion therapy in detail. It was also interesting to learn about Dr. Funk’s rational for using turmeric instead of curcumin. She stated that turmeric “contains essential oils and are better absorbed” in comparison to curcumin. In the future it would be interesting to see if this turmeric stroke study has similar effects as the curcumin metabolic syndrome study. Hopefully Dr. Funk’s team uses a more reasonable amount of turmeric in their studies. Regardless it is difficult to directly compare the two studies because they use different animal models and focus on different diseases. Hopefully Dr. Funk’s turmeric studies find a new treatment for this tragic disease which continues to take the lives of millions of people every year.

Weisberg’s article concerning curcumin’s affects on obesity, diabetes and inflammation

http://www.ncbi.nlm.nih.gov.ezproxy1.library.arizona.edu/pubmed/18403477

New study which examines the relationship between turmeric and stroke

http://azstarnet.com/news/science/article_6b776950-2e1e-56b6-ac9d-aad1bb35ac5c.html

MRI can detect early stages of Rheumatoid Arthritis

Currently the most common form of imaging used for the assessment of rheumatoid arthritis is radiography (X-rays). However, in a recent study which examined the effectiveness of the immunosuppressant golimumab in the treatment of rheumatoid arthritis, the research team used magnetic resonance imaging (MRI) to monitor the progress and improvement of the patients while on this drug. They saw that the MRI images allowed them to measure inflammatory lesions (ie. synovitis) and erosions, which they would not have been able to do with X-ray images. Most importantly, the MRI images were able to show pre-erosive changes, that occur before irreversible joint damage occurs. Other studies have also shown that MRI's provide a much more accurate assessment of RA.

Radiography is still being used most frequently however, mostly because it is cheaper and easily reproducible. Also because it makes serial comparison much easier for disease assessment. MRI is much more expensive but it is currently being developed as a treatment tool since it has the crucial ability to detect the disease early, at a stage at which disease-modifying drugs can be used. This is therefore an important tool in potentially the treatment of RA, and also in research of new drugs that may target the early stages of rheumatoid arthritis, before irreparable joint damage occurs.

• Conaghan, PG, P.Emery, M. Ostergaard, EC Keystone, MC Genovese, EC Hsia, W. Xu, and MU Rahman. "Assessment by MRY of Inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: Results of the GO-FORWARD trial." Ann Rheum Dis 11 (2011): 1968-74. Print.
• http://www.diagnosticimaging.com/mri/content/article/113619/1976582
• http://emedicine.medscape.com/article/401271-overview

Xigris Pulled From Market

Yesterday was a great day for evidence-based medicine. In light of what should be the definitive nail in the coffin, Eli Lilly has decided to pull Xigris (drotrecogin alfa activated) from the market. This drug represented an innovative and promising approach to the treatment of severe sepsis, but it seemed doomed from the outset. I'm certain that I am not alone in my amazement that it has been on the market for so long.

Sepsis is an overwhelming systemic inflammatory response to infection, characterized by high systemic levels of proinflammatory cytokines, such as IL-1b, IL-6, IL-8, and TNF-a. By numerous mechanisms - some known, probably more unkown, this results in a variety of organ system failures - cardiovascular, respiratory, hematologic, neurologic, renal, and hepatic. The mortality rate ranges, depending on the number and severity of organ failures, from 20 to 60 percent. Treatment of sepsis is largely comprised of treatment of the underlying infection and supportive care (fluids, vasopressors, artificial respiration, dialysis) for organ failures. Naturally, when a novel therapy for severe sepsis came along, the critical care community, desperate for a new idea, embraced it with open arms.

The theory behind drotrecogin, which is a recombinant human activated protein C (rhAPC), is that by modifying the complex interaction between the clotting cascade, the intrinsic fibrinolytic system, and the inflammatory response, outcomes in sepsis could be improved. Activated protein C inhibits coagulation by inactivating factors V and VII leading to reduction in thrombin generation. It promotes fibrinolysis by inactvating PAI-1 (Plasminogen Activation Inhibitor) and preventing activation of TAFI (Thrombin Activatiable Fibrinolysis Inhibitor). Finally, it exerts antiinflammatory effects by supression of adhesion (also dependent upon the clotting cascade) and cytokine release by activated leukocytes.

PROWESS was an industry-funded (Eli Lilly), multicenter phase III clinical trial in which patients with severe sepsis (sepsis with at least one organ failure) were randomized to receive a 96 hour infusion of rhAPC or placebo. The results were impressive - a reduction in mortality from 30.8% in the placebo group to 24.7% in the treatment group. Almost immediately, however, the story began to unravel.

PROWESS is likely the most widely criticized clinical trial in the critical care literature. The relatively small size of the trial is of concern. More importantly, however, the study protocol was changed midstream. They changed the master cell bank from which the recombinant protein was derived. The eligibility criteria were amended to discourage enrollment of patients with serious pre-existing illness. Even the placebo was changed. Curiously, the efficacy of treatment with rhAPC was greater after these changes were made. Despite the above concerns, and despite the split vote by the FDA advisory panel (10-10), the FDA elected to approve rhAPC for use in the treatement of severe sepsis.

The more deeply this drug was studied, the less support it found. Post-hoc analyses suggested that less ill patients may actually have an increased risk of harm, be it serious bleeding or even death. The ADDRESS trial prospectively studied rhAPC in patients with low risk of death. Not only were the mortality rates similar betwen groups (17% vs. 18.5%), but mortality in the placebo group was substantially lower than that of similar placebo patients in the PROWESS trial. ENHANCE was an open label trial to look in more detail about the mortality and morbidity rates in treated patients; mortality was similar to PROWESS, but the risk of severe bleeding events was significantly increased. A subsequent large meta-analysis pooled data from five major trials and found no statistically significant benefit to the administration of rhAPC in severe sepsis.

In 2007, the European Medicines Agency (EMA) determined that further clarification of the risk/benefit balance of rhAPC was required. The PROWESS-SHOCK trial addressed this issue. It enrolled similar patients to those in the original PROWESS study, but with more stringent criteria. Patients were required to be in vasopressor-dependent septic shock through the 8-hour pretreatment and subsequent enrollment periods, and were required to have at least one other manifestation of end-organ hypoperfusion (decreased urine output, metabolic acidosis, hepatic dysfunction). Interim analyses were permitted for adjustment of sample size, but early efficacy termination was not permitted after the first analysis (as it was in PROWESS). Futility termination was also not permitted, but termination due to apparent harm was at the discretion of the data monitoring committee.

This study is, perhaps, the most rigorously designed trial in the history of critical care. The manuscript has yet to be published, but the results are incontrovertible - 26.4% mortality in the rhAPC vs. 24.2% in the placebo group. This validates the concerns of critics of PROWESS and confirms the findings of numerous trials and meta-analyses published since PROWESS. As a result, Lilly has removed Xigris from the market. Lilly's Chief Medical Officer, Dr. Timothy Garnett understandably, and incorrectly, identifies improvement in the standard of care for patients with severe sepsis as the reason for the disparity between PROWESS and subsequent trials. Were that the case, the improved standard of care would apply to both groups, lowering overall mortality while preserving the statistically significant difference between them. If anything, the opposite hapened - a statistically insignificant trend towards harm associated with the administration of rhAPC.

I sincerely hope that the FDA stands up and takes notice - and responsibility for their mistake. This is only the latest in a long series of black marks against an agency that seems to be able to do no right. Clearly, the drug approval process needs to be modified, and if nothing else, approval needs to be conditional pending confirmatory studies and intensive post-approval surveillance.

Vaccinations for Cancer

For the past several decades, countless studies of been conducted in hopes to finding a vaccine that will allow our immune system to recognize carcinogenic cells and destroy them. Though the FDA still not yet approved most of them them, numerous clinical trials are currently in progress. As of now there are two main types of cancer vaccinations. The first type is Preventative vaccines which are intended for health individuals with no cancer and the second type are Treatment vaccines intended for individuals with already existing cancer. These sets of vaccination belong to a class of medication called Biological Response Modifiers where the ultimate goal is to stimulate and restore the body’s ability to fight off infections. At first researchers thought that similar to other vaccinations like Measles and Mumps, the vaccination would allow the immune system to recognize specific cancerous cell thus preventing infection, but because carcinogenic cells mutate so rapidly it is impossible to create a good response vaccine. This is where Preventative vaccinations come into play. Instead of targeting cancerous cells, these vaccinations target viruses, bacterium, and parasites that lead to cancer.

As of now, the U.S. Food and Drug Administration has only approved two preventative vaccinations Gardasil and Cervarix, these two vaccines are used to prevent two types of Human Papillomavirus (HPV) which causes about 70% of all cervical cancer cases worldwide. Protecting against HPV may also prevent vulvar, vaginal, anal, and oropharyngeal cancers. Other types of targeted organisms include Hepatitis virus B & C which can cause various types of liver cancers, helicobacter pylori a bacterium that causes stomach cancer and parasites such as schistosomes which causes bladder cancer. Visit site

http: //www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines to see full list.

Lastly, there are the treatment vaccines used to treat patients that are already diagnosed with cancer. These are sometimes called True Cancer Vaccines and are only specific from person to person. They are meant to trigger a person’s own specific response in which the body will then attack cells with one or more specific antigens. The goal of these vaccines is to delay or stop cancer cell growth causing the tumor itself to shrink and prevent the cancer from coming back into the system. Last year, FDA has approved the first cancer treatment vaccine called Provenge. This vaccine is made for men with metastatic prostate cancer and is designed to stimulate an immune response to prostatic acid phosphatase (PAP) which is an antigen found in prostate cancer cells. Since this treatment is specific from patient to patient, how the vaccination process works is first white blood cells are extracted from the patient and exposed to PAP. Then, the white blood cells are infused back to the patient via vein. This process is repeated two more times, two weeks apart. The goal is to stimulate an immune response to recognize the PAP antigen. So far, this clinical trial shows good response.

Sources:

http://www.cancer.org/Treatment/TreatmentsandSideEffects/TreatmentTypes/Immunotherapy/immunotherapy-cancer-vaccines

http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines

Murphy KM, Travers P, Walport M, editors. Janeway's Immunobiology. 7th ed. New York: Garland Science, 2007

Osteoarthritis and Glucosamine

In 2002 a study was done to compare the effects glucosamine and chondroitin sulfate to the prescription pain relief celecoxib (a NSAID). The study was coordinated by the School of Medicine at the University of Utah and involved 16 study centers across the United States. The study was funded by two branches of the National Institute of Health (NIH): National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). A link to the NIH general public release about the study is here: http://nccam.nih.gov/research/results/gait/D310_BKG.PDF.

The study found that for moderate to severe pain the glucosamine and chondroitin sulfate treatment provided statistically significant pain relief when compared to the placebo; the prescription medication also had statistically significant pain relief. For participants with mild pain, the glucosamine and chondroitin treatment provided no statistically significant pain relief.  The study also found that the glucosamine/chondroitin treatment was not effective at slowing the rate of cartilage loss when compared to the placebo treatment.

The conclusion of the study is that glucosamine/chondroitin treatments may be as effective in osteoarthritis pain as prescription NSAID treatments. However, there was no evidence to support the claims that glucosamine/chondroitin treatments can either help rebuild cartilage or slow the rate of cartilage loss.

Omega 3 Fatty Acids and Rheumatoid Arthritis - Fact or Fiction?

Many of the lay articles we discussed in class presented dietary supplements that were supposed to help with arthritis treatment. Since we usually cannot cure arthritis completely, treatment tends to focus on reducing pain, improving function, and preventing further joint damage. The drugs that are recommended and prescribed to treat arthritis can cause serious side effects (such as bleeding ulcers, stomach problems, etc) and still may not be completely effective in eliminating pain. For this reason, many people with arthritis are desperate to find anything that will help them reduce pain and regain function and are willing to try just about anything (including Zymosine?). Many diets and supplements have been proposed as the new cure for arthritis, yet few are backed by scientific evidence. One supplement that everyone seemed to be suggesting was omega 3 fatty acids, so I thought I would look into it a little more since it seemed promising.

There have actually been quite a few studies conducted on this topic. For the most part, they all seem to agree that omega 3 fatty acids DO have some anti-inflammatory properties. One double-blind study of patients with active RA examined the effects of fish oil capsule supplements in addition to the standard arthritis medications and concluded that fish-oil consumption resulted in the improvement of RA symptoms and a reduction in neutrophil leukotriene B4 production. Another study looked at the long-term effects of omega 3 fatty acid supplementation in people with rheumatoid arthritis and found that a daily intake of 2.6 gm results in significant improvement and may reduce the need for concomitant anti rheumatic medication. Several other studies I read had similar results. Therefore, it does seem that an omega 3 fatty acid supplement may be helpful to people with rheumatoid arthritis - the question that remains now is that of dosage. We still are not sure the dosage that is recommended to produce significant improvement for patients. Further studies need to be conducted to determine this (although the above study suggests 2.6 grams/day so that may be a good approximation).

Sources:

Geusens, Piet, Carine Wouters, Jos Nijs, Yebin Jiang, and Jan Dequeker. "Long-term Effect of Omega-3 Fatty Acid Supplementation in Active Rheumatoid Arthritis." Arthritis & Rheumatism 37.6 (1994): 824-29. Print.

Kremer, JM, W. Jubiz, A. Michalek, RI Rynes, and LE Bartholomew. "Fish-Oil Fatty Acid Supplementation in Active Rheumatoid Arthritis." Ann Intern Med. 4 (1987): 497-502. Print.

Proudman, Susanna M., Leslie G. Cleland, and Michael J. James. "Dietary Omega-3 Fats for Treatment of Inflammatory Joint Disease: Efficacy and Utility." Rheumatic Disease Clinics of North America 34.2 (2008): 469-79. Print.

Sex and Immunity 2

While choosing the title to my last post, I was keenly aware that at least a few people were probably hoping for a more interesting post about actual sex, not just our biological gender.

Well, this one’s for you! 

Psychologists at Wilkes University in Philadelphia reported a “boost” in the immune system of people reporting moderate sexual activity after relating IgA levels to the frequency of sexual encounters of 111 undergraduate students.  They found students who reported having sex 1-2 times a week had over a 30% increase in levels of IgA than students who reported abstinence.  Interestingly, students who reported having sex 3+ times a week had LOWER levels of IgA than the abstainers.  Here’s the BBC article:

http://news.bbc.co.uk/2/hi/health/319070.stm   

Admittedly, I haven’t done any research beyond this one article, but I did find the results interesting.  It makes sense that sex increases your exposure to pathogens and thus antibody levels would increase.  But what if there is another affect?  It would be interesting to repeat this study and compare monogamous couples with singles who have frequently new partners, or partners who live together and share the same pathogens with those who don’t. 

I also think the comment on why students who reported having sex 3+ times a week had lower IgA levels brings up an interesting point:

"My feeling is that the people in the very-frequent-sex group may be in obsessive or poor relationships that are causing them a lot of anxiety.  We know that stress and anxiety make IgA go down."

Obviously, this guy is trying to justify the odd results in the 3+ group, and you certainly can’t assume that a relationship in which the partners are having sex 3+ times a week is automatically “obsessive or poor.”  But this does present a rather overwhelming subject matter – exactly how do our behaviors, attitudes, emotions, and environment affect immunity?  And how can we concretely measure and understand those effects?

Sex and Immunity

If you were to pit a man’s immune system against a woman’s, who would get the edge?  The answer – most likely the woman.  Women’s immune systems are generally stronger and respond better to pathogenic stimuli, including viral, bacterial, fungal, and parasitic diseases, than men’s.  For example, studies show that in surgical patients with severe sepsis (defined as systemic inflammatory response + infection + organ dysfunction), women have a significantly higher survival rate (74%) compared to men (31%).  Additionally, incidence of severe sepsis is significantly lower in female ICU patients than male in nearly all age groups.  Ironically, the same mechanisms that enable women with this immunological survival advantage also increase their susceptibility to autoimmune disorders, such as systemic lupus, multiple sclerosis, and rheumatoid arthritis. 

Sex-based differences in disease and the immune system’s response are attributable to several mechanisms, including anatomy, differential expression of steroid hormones, X-chromosome inactivation, and life and gender-specific experiences.  For instance, estrogens have multiple roles influencing immunocompetence.  Estrogen receptors are expressed on T cells, B cells, dendriditc cells, macrophages, neutrophils, and natural killer cells.  The estrogen ligand/receptor complex on these cells gets translocated to the nucleus where is regulates transcription.  Estrogens have anti-inflammatory effects on monocytes and neutrophils, they increase numbers of Treg cells during the follicular phase of the menstrual cycle, and they affect expression of some chemokine receptors (chemokine receptor 5 is upregulated by estrogens, an interesting connection to our discussion about the mechanism of infection of HIV).  Additionally, estrogens have several affects of B cells, including enhancing polyclonal activation, which leads to higher IgM and IgG serum levels. 

A significant number of genes involved in immunity are located on the X chromosome.    Because of this, women can also gain immunological advantages from X-inactivation.  X-inactivation is the silencing of one X chromosome in females, resulting in female mosaicism – every cell in a female body has either one or the other X chromosome inactivated.  This actually allows females to cope with recessive mutations or other vulnerabilities introduced by one of their X chromosomes.  However, males have only one X chromosome and no saving grace if they end up with an undesirable allele. 

A group from Ghent University in Belgium recently hypothesized that this same phenomenon in X-linked microRNAs involved in immunity could also lead to sex-specific immune responses.  MicroRNAs (miRNA) are important negative regulators of protein expression and function and act by targeting and degrading mRNA transcripts.  There are a number of known miRNAs on the X chromosome directly involved in immune functions; however, there are no miRNAs on the Y chromosome.  MiRNAs are upregulated during chronic inflammation and, interestingly, the deletion of Dicer (the key enzyme for miRNA processing) leads to reduced T cell numbers and a complete arrest in B cell maturation.  Could these X-linked miRNAs also contribute to the immunological advantage of females and/or their predisposition to autoimmune diseases? 

Just some food for thought.  Men vs. Women.  A battle of immune systems.   

Fish EN.  2008.  The X-files in immunity: sex-based differences predispose immune responses.  Nature Reviews Immunology 8: 737-744.

Pinheiro I, Dejager L, Libert C.  2011.  X-xhromosome-located microRNAs in immunity: Might they explain male-female differences?  Bioessays.

Rheumatoid Arthritis and the remission phase!

Rheumatoid arthritis has been found very hard to treat because we are not sure of the initial causes. But the ultimate goal for anyone with this disease is to be pain free or be in the “remissive” phase. “Remission is defined as having no tender or swollen joints for at least three months and have fewer than 15 minutes of morning stiffness”. While it is rare for patients to achieve spontaneous remission (getting better on your own with no remaining symptoms), partial remission is far more common with the help of treatment. The most recent treatments have been to administer synthetic compounds that mimic the effects of antioxidants like tempol or M40403. With these, the hope is to convert O2 radical to H2O2 at a higher rate, thus getting the destructive chemicals out fast, and doing minimal damage.

I came across an article in the journal of Arthritis and Rheumatism that discussed how important it is to treat very early or at the first signs of rheumatoid arthritis. This study was conducted on 534 early RA diagnosed human subjects that treated and adjusted treatment depending on a Disease Activity Score of 28 different joints. They hoped that by using the “treat-to-target” or adjusting treatments with their pain scale over time could help put more patients into remission earlier. After analyzing the data after a 6-month and 12-month period, they found that with their treatment, 58.1% of the patients went into DAS28 remission after a year. With the help of different scales like the EULAR model, radiographic data and medication, this study showed that “treat-to-target” is a very reachable goal for the clinical setting. By treating a randomized sample, they hoped that this method could be used further for the general public in order to help alleviate the pain associated with rheumatoid arthritis.

http://onlinelibrary.wiley.com.ezproxy2.library.arizona.edu/doi/10.1002/art.30494/full

Mandatory HPV Vaccination in Schools

Upon investigating information about Gardasil, a vaccine against human papillomavirus (HPV), I came across this great article discussing the HPV vaccination and its requirement in schools. HPV is the most common sexually transmitted infection (STI) worldwide and can cause genital warts and cervical cancer. In 2006, the FDA approved Gardasil, a quadrivalent vaccine against some of the strains of HPV. After its approval, several states have passed laws making HPV vaccination mandatory for minor girls to enter school (middle or high school). Other legislation that has been passed in some states with regard to the HPV vaccination include providing state funding to defray or eliminate the cost, educate the public, and establish committees to make recommendations about the vaccination.

It seems unwise to mandate a vaccine in schools when it hasn’t even been approved for very long. Additionally the HPV vaccination is against an STI which as its name implies is transmitted sexually. Why should we make every young woman be vaccinated when she may not even be sexually-active? HPV is not typically transmitted in school, at least not in the way other diseases are transmitted. This vaccination is different than others that are mandated which are against diseases that are highly contagious and/or associated with significant morbidity and mortality. Furthermore, the long-term safety and effectiveness of the HPV vaccine are not clear. There have been several cases reported of severe adverse effects, including death in patients that were administered the HPV vaccine. Also, HPV is not immediately life-threatening. Considering all these reasons along with additional information mentioned in the article I don’t think we should make HPV vaccination a requirement in school-aged children.

I do believe vaccinations are beneficial and the ones that are currently mandated for school attendance are appropriate. My only concern is in implementing the HPV vaccine as a requirement for school attendance without more research and evaluation of the long-term effects. It doesn’t seem fair to require grade-school children to take a vaccination when all the risks haven’t been fully evaluated. Currently parents can opt-out of the HPV vaccination, but why make it a requirement in the first place? Although the HPV vaccination seems promising, it shouldn’t be mandated in schools.

Article Link

http://www.ncbi.nlm.nih.gov/pubmed?term=Assessing%20Mandatory%20HPV%20Vaccination%3A%20Who%20Should%20Call%20the%20Shots%3F