05 November 2009

Leishmaniasis and Arginase Activity

Leishmaniasis is a vector-born disease, which causes uncontrolled parasite (Leishmania) growth. This disease is predominantly seen in children and is “endemic in almost all tropical and subtropical areas” (Muller, et.al. e235). Leishmania predominantly live in macrophages, in which the macrophages can control the growth and production of these parasites through two enzymes, NOS2 and arginase. Furthermore, these macrophages are M2 macrophages, which are regulated by Th2 cells. These researchers have shown that increased arginase activity leads to non-stop parasite growth as well pathology in vivo (e235).

Researchers hypothesize that arginase activity is increased in children, which accounts for the severity of Leishmanisis in children. Balb/c mice were used in various age ranges and were infected with Leishmanisis and then tested to determine arginase levels. The researchers showed the younger mice had increased levels of arginase than the older mice. Furthermore, the younger mice had more exacerbated pathology as well as increased severity of lesions. Because Balb/c mice lack the proper Th1 response in the presence of Leishmania, the researchers performed several other experiments to show that the improper regulation of Th1 was not the cause of the increased parasitic growth. They were able to show that the decrease in arginase activity with age is responsible for the the severity of Leishmaniasis in children.

This article is interesting because it shows the older people are less prone to this disease than children, which is generally the opposite of most diseases since ageing results in a decrease in immune responses. However, arginase is also known to play an important role in wound healing. One would expect that children would have an increase in arginase due to their more active lifestyles and because they generally get hurt a lot more than older people. This makes me think that at one point, arginase might not have been the primary cause of parasite overgrowth, but it evolved into a parasite growth promoter.

Also, it seems that there would be even more severe problems in children that lacked the proper M1, classically-activated macrophages because they would not be able to destroy the parasites and control the infection. This would make it nearly impossible for M2 macrophages to try to help with the healing process. Although, there is paper doesn't show a correlation between the Th phenotype and the severity of the disease, I wonder whether all people with Leishmanisis might have reduced efficiency of their M1 macrophages, which contributes the overall problem with the disease.


"Age-related alteration of arginase activity impacts on severity of leishmaniasis." Müller I, Hailu A, Choi BS, Abebe T, Fuentes JM, Munder M, Modolell M, Kropf P.PLoS Neglected Tropical Diseases. 2008 May 14;2(5):e235.

03 November 2009

UN urges nations to lift HIV travel ban

I came across this article and found it interesting. I had no idea that America has banned anyone from entering the US if they have HIV/AIDS. It seems rather archaic to ban anyone because they have the disease. It has no public health threat. I am glad that this ban is being lifted.

 UN urges nations to lift HIV travel ban

(AFP) – 2 days ago

UNITED NATIONS — UN chief Ban Ki-moon hailed US President Barack Obama's removal of a decades-old travel ban on HIV-positive visitors, and urged other countries to do the same."I congratulate President Obama on announcing the removal of the travel restrictions for people living with HIV from entering the United States," Ban said on Saturday in a statement released by UNAIDS, the Joint United Nations Program on HIV/AIDS."I urge all other countries with such restrictions to take steps to remove them at the earliest."Obama announced his administration would overturn on Monday a controversial US policy that had been in place since 1987. The ban on foreign nationals with HIV/AIDS visiting the United States will effectively be lifted early next year."Such restrictions, strongly opposed by UNAIDS, are discriminatory and do not protect public health," the program said. Ban has made the lifting of stigma and discrimination connected with AIDS a personal mission, first calling on countries to lift their travel restrictions in 2008 at a UN meeting on the disease. The travel restrictions "should fill us all with shame," Ban told a global AIDS conference in August 2008.According to UNAIDS, Ban's home country of South Korea is "in the last stages of removing travel restrictions," while China and Ukraine are among countries considering following suit."Placing travel restrictions on people living with HIV has no public health justification. It is also a violation of human rights," said UNAIDS executive director Michel Sidibe. On Friday, as he signed a bill reauthorizing funding for a federal program providing HIV-related health care, Obama announced the repeal of the travel ban, describing the 22-year-old policy as a "decision rooted in fear rather than fact.""If we want to be the global leader in combating HIV/AIDS, we need to act like it," Obama said."And that's why on Monday, my administration will publish a final rule that eliminates the travel ban effective just after the New Year."Obama's predecessor, George W. Bush, signed legislation last year that removed HIV from a list of diseases "of public health significance" that effectively barred any person infected with HIV from entering the United States. But the law was not implemented by the US Department of Health and Human Services, which regulates US immigration authorities in some instances.

http://www.google.com/hostednews/afp/article/ALeqM5jjO8WkZTKon6BE60rzWcHJEr0Fgw

Joint Popping Myths

Has anyone else grown up with parents and grandparents that always scolded “don’t crack your knuckles you will end up with big huge arthritic joints when you are my age…” I know I have which lead me to do a little research on this particular topic.

Joints can “crack” or “pop” for various reasons. When a person pops their knuckles a bubble is being formed in the synovial fluid of the joint. When a person is able to crack their neck or back, ligaments and tendons are sliding over a bump or the edge of a bone. These are both perfectly normal sounds to make. But then there are also various injuries that can also cause a cracking or a popping sounds to occur with everyday movement of a joint. Injuries that involve torn cartilage (such as in a knee joint) will allow the joints to lock up periodically and the wiggling that a person has to do to resolve this can result in a pop. Also if a person has almost any form of arthritis, the will also experience the cracking and popping sounds of joints. This is caused by having deteriorated cartilage and bones that will make noises when articulated regardless of range and quality of motion.

The former two examples are not harmful to the body, and a lot of times cracking or popping joints is a way to relieve a little tension from the body; I know that is why I do it. Right now I have not seen clinical evidence saying that arthritis can indeed be caused by joint popping, but continuous joint popping and articulating the joints out of their normal range of motion probably does not have a huge health benefit, and as with all bad habits there is potential to find out that it could cause problems later in life, plus its annoying to hear the person sitting next to you constantly cracking their knuckles….

The latter two examples are ones that we already know has ad inflammatory component that plays a critical role in the cracking and popping din that is coming from the joints. These examples show that the noises are caused by arthritis or some other injury and not the other way around.

I got my information from the University of Washington Orthopedics and Sports Medicine website at http://www.orthop.washington.edu/.

02 November 2009

Humira: beneficial or detrimental?

Humira (adalimumab) is a drug used for the treatment of inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and Crohn’s disease. Humira is a recombinant human IgG1 monoclonal antibody specific for human TNF alpha. Blocking the actions of TNF alpha has been shown to reduce the inflammation associated with inflammatory diseases. While TNF alpha inhibitors have proven to be a very effective therapy for inflammatory diseases, they also increase the patient’s risk of developing severe and even fatal infections. A patient using Humira is more susceptible to infections including tuberculosis and infections caused by viruses, fungi, or bacteria. Other possible side effects include certain types of cancer, allergic reactions, nervous system problems, blood problems, heart failure, and various immune reactions.

Despite the risk for serious infections and other harmful side effects, Humira has been proven to inhibit joint damage in patients with rheumatoid arthritis when taken early in the course of the disease. They were also less likely to experience further damage multiple years later. Many patients who take Humira are able to achieve clinical remission from their inflammatory disease. In most studies, Humira is found to be effective and well-tolerated by patients suffering from an inflammatory disease.

Humira appears to have significant benefits but also potentially fatal side effects. Before taking Humira, it is important for the patient to weigh the costs and benefits of the drug.

01 November 2009

The Difference Between Osteoarthritis and Rheumatoid Arthritis?

You knew this topic was coming. So what is the difference?

Osteoarthritis (what we generally think of when speaking of arthritis) is also dubbed the wear-and-tear arthritis, named such because it involves the wearing down of joint cartilage due to aging and overuse. The cartilage serves as a shock-absorber and cushion between two bones of a joint, and as it breaks down the bones may come into direct contact with each other resulting in severe pain. It is the most common form of arthritis, with 21 million Americans afflicted with the disease. Interestingly, although osteoarthritis is not an inflammatory disease, as the “-itis” ending may lead us to believe, the immune system does have a role with cytokines IL-1 and TNF-α, in addition to NO and prostaglandin E2, posing as the suspects. Surely, there is also local inflammation at the site of the disease as well. This condition is commonly brought about by injury (such as a sports injury), but can also be instigated by weak muscles, obesity, or plain heredity. There is no known cure for this disease, and it is currently the leading cause of chronic disability in the United States. This is scary considering I had previously sustained two tears in my lateral meniscus of my left knee, and underwent surgery just this summer to fix it. The orthopedic surgeon excised 40% of my meniscus (a substantial amount), and he seemed to be of the notion that I would not be at additional risk of acquiring arthritis because of it. All I can say is that I hope he's right!

Now, rheumatoid arthritis is clearly a chronic, inflammatory disease, where the body's immune cells attack the host's own healthy tissues (the characteristics of an autoimmune disease). In response to this, the white blood cells rush to the synovium and start the inflammatory process. Thus, the distinguishing characteristic between rheumatoid arthritis and other forms of arthritis is that the inflammation takes place at the synovial membrane, where swelling usually is caused by the buildup of synovial fluid (in the knees or fingers, e.g.). Rheumatoid arthritis tends to affect the smaller joints first, and can spread throughout the body. A tell-tale sign of this disease is morning stiffness of the joint for 30 min to one hour (following sleep), followed by a gradual alleviation with activity. The causes are not clearly known, and there is also no cure for this one yet.