Hope for Sickle Cell

Sept. 19, 2014

By Medical Discovery News

While sickle cell disease has long been studied, a recent discovery revealed that the disease significantly increases the levels of a molecule called sphingosine-1-phosphate (S1P), which is generated by an enzyme called sphingosine kinase 1 (SphK1). Inhibiting the enzyme SphK1 was found to reduce the severity of sickle cell disease in mice, which will hopefully lead to new drugs that target SphK1in order to treat sickle cell disease in humans.

Sickle cell disease is caused by a change in the gene that is responsible for a type of hemoglobin, the protein molecule in red blood cells that carries oxygen. This tiny change results in hemoglobin clumping together, changing the shape of red blood cells.

The name for sickle cell disease actually comes from misshapen red blood cells. Rather than being shaped like a disk, or a donut without a whole, sickle cells are shaped like a crescent, sort of bending over on themselves. The normal shape is critical to red blood cells’ ability to easily travel through blood vessels and deliver oxygen to cells and tissues. Sickle cells become inflexible and stick to each other, blocking the flow of blood through blood vessels.

Symptoms of the disease begin to appear at about four months of age. Normally, red blood cells live for about 120 days. Sickle cells only survive 10-20 days. Although the bone marrow tries to compensate for the rapid loss of red blood cells, it cannot keep up. The disease causes pain, anemia, organ damage, and possibly infections.

Although the symptoms and their severity vary, most people with sickle cell disease will have periodic crises lasting hours or days. Symptoms include fatigue, paleness, shortness of breath, increased heart rate, jaundice, and pain. Long-term damage can occur in the spleen, eyes, and other organs, and sickle cell disease increases the risk of stroke. People who only inherit one copy of the sickle cell hemoglobin gene have a milder case of the disease than those who inherit two copies, one from each parent.

Current treatments only reduce the number and the severity of crises using hydroxyrurea, blood transfusions, pain medications, and antibiotics. As the disease advances, dialysis, kidney transplants, eye surgeries, gall bladder removal, and other treatments may be necessary. The only cure for the disease is a bone marrow transplant, which is not an option for everyone.

So it’s pretty exciting that when scientists found that levels of S1P were elevated in mice with sickle cell disease, they inhibited the enzyme SphK1 to reduce the levels of S1P. As a result, red blood cells lived longer and had less sickling. The mice also had less inflammation and tissue damage, which would reduce damage to red blood cells and prevent symptoms of the disease. When they engineered sickle cell disease mice without the gene for the enzyme SphK1 that makes S1P, again the mice had less sickling and symptoms.

How does S1P influence sickling? Apparently, it binds directly to hemoglobin and reduces its ability to collect and carry oxygen, which causes the characteristic folding of cells. S1P has other roles in the body, so it is unknown whether inhibitors to SphK1 can safely and effectively be used in humans to treat sickle cell disease.

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The Relationship Between Sweat and Sleep

Jan. 10, 2014

By Medical Discovery News

Sweat and sleep

If only getting to sleep were really as easy as counting sheep. Over half of Americans admit to struggling with insomnia a few nights a week. And the loss of sleep doesn’t just make a person tired, it can affect how long they live. People who an average of six or fewer hours of sleep each night had higher mortality rates than those who slept seven or more. New research has provided more insight into how people can overcome or prevent insomnia.

Problems falling asleep initially, waking up during the night and then having problems getting back to sleep, feeling tired upon waking in the morning, and waking up before the alarm all count as insomnia – it’s both the ability to fall asleep and stay asleep. There are two different types: primary, a direct issue with sleep, and secondary, sleep issues caused by an underlying medical condition like depression, asthma, and overuse of alcohol. Insomnia can lead to other serious medical issues including memory problems, depression, heart disease, and car accidents. 

Common causes of insomnia include stress, emotional issues, physical discomfort, medications, disruptions in a person’s schedule, and environmental disturbances like light, noise, and temperature. Many suffering from insomnia rely on medications such as sleeping pills and sedatives, the most common being over-the-counter antihistamines. But these drugs can come with significant side effects, particularly for the elderly. Cognitive behavioral therapy, which changes ways of thinking to improve behavior, is recommended for insomnia.

Evidence shows the best ways to prevent insomnia are to maintain a regular schedule, avoid caffeine for the eight hours before bed, and especially get some exercise. While research has long shown the positive relationship between exercise and sleep, a recent study has led scientists at Northwestern University to conclude that sleep may influence exercise more than exercise influences sleep.    

This experiment involved a group of women diagnosed with insomnia, divided into two groups: an exercise and an inactive group. The exercise group performed 30 minutes of moderate exercise several times a week for 16 weeks while the other group was inactive. The results were encouraging, since those in the active group slept 45-60 minutes longer each night, woke less frequently, and felt more energized during the day. 

The surprise came when the scientists took a detailed look at the diaries the women kept of their exercise and sleep. The effect of exercise seemed to take longer than expected – a full four months. Also, most did not report sleeping better on the nights after they exercised, but that a good night’s sleep helped them exercise better the next day. 

People without sleep issues typically experience a more restful night’s sleep after exercising, so why is this not the case for people with insomnia? It may be that those with sleep disorders are different neurologically. They may have hyper-arousal of the stress system, which takes a prolonged regular exercise regime to overcome. Further research will be able to answer remaining questions about the timing or intensity of exercise, the effect of different types of exercise, and whether this is the case in men as well.

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