Genetic links about migraine

Migraine is an intense headache, which can last from several hours to several days (3 days). When a person has a migraine, he or she can no longer perform daily activities. No one knows why some people are more prone to migraine than others, but there seems to be a familial aggregation. Now researchers at the Wellcome Trust Sanger Institute have discovered for the first time that in the onset of migraine are involved five genetic regions.

In the largest study on migraine, researchers have tried to identify what are the mechanisms underlying the susceptibility to migraine. They found 12 genetic regions: 8 of them appear to be involved in the control circuits in the brain and two of these regions appear to be associated with maintaining brain health. It seems that genetic susceptibility to migraine depends on these pathways. In fact, it seems that there are also other regions involved as researchers found  more than 130 genetic regions implied in susceptibility to migraine but without statistical significance.

Statistics show that 14% of people suffer from migraine, moreover the Global Burden of Disease Survey 2010 points out that migraine is responsible for the highest costs among neurological disorders. Migraine is a condition difficult to study because there are no some specific biomarkers in patients suffering from migraine.

Migraine

Dr Aarno Palotie, from the Wellcome Trust Sanger Institute, said that this study gave very useful information about the cause of migraine.  Dr. Palotie added that migraine and epilepsy are two neurological conditions extremely difficult to investigate biochemically because the patient is perfectly healthy between crisis. “The molecular mechanisms of migraine are poorly understood. The sequence variants uncovered through this meta-analysis could become a foothold for further studies to better understanding the pathophysiology of migraine” Dr Kári Stefánsson, President of deCODE genetics, points out.

To get to discover the genetic regions underlying migraine, researchers used more than 100 000 samples from both migraine patients and patients without migraine. What they did was to compare the results from 29 different genomic studies and found that these susceptibility regions are connected with a network of genes that are involved in oxidative stress. It is possible that genes in these genomic regions to be interconnected and to interfere with the internal control of brain circuits. Dr Mark Daly, from the Massachusetts General Hospital and the Broad Institute of MIT and Harvard, said that this approach is the most effective way to understand the biology of these neurological disorders.

Multiple endocrine neoplasia type 1

MEN means multiple endocrine neoplasia and is an autosomal dominant syndrome. In fact, MEN refers to the combination of several different syndromes caused by tumors (benign or malignant) of endocrine glands. Von Hippel Lindau, McCune Albright syndrome and Carney complex could also be considered part of MEN, because they are all autosomal dominant syndromes that includes endocrine tumors and because they have a clinical features which overlap with MEN syndromes.

Types of multiple endocrine neoplasia

There are three types of MEN: MEN1 ( also called Werner syndrome) – pancreatic neuroendocrine tumors, pituitary adenoma, and adenoma or hyperplasia of parathyroid with or without angiofibromas.

MEN 2A syndrome (or Sipple syndrome) includes medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism.

MEN 2B or MEN 3 (or Shimcke syndrome) includes medullary thyroid carcinoma, pheochromocytoma and neuromas.

It should be noted that MEN is a rare syndrome, each of the two syndromes MEN ( MEN 1 and MEN 2) affects 1 in 30 000/40 000 persons. Among the subtypes of MEN, MEN 2A is the most common and 2 B is the rarest.

Neoplasia

Multiple endocrine neoplasia type 1

Approximately 70-95% of patients with MEN 1 has a MEN1 gene mutation. This gene encodes menin, which is a tumor suppressor, which means it prevents the cells to divide uncontrollably. When the MEN 1 gene mutations occur, it cannot exercise its function and different tumors appear ( parathyroid, pancreatic or pituitary).

Signs and symptoms begin to appear around the age of 20 years (50% of patients) and by the age of 40 years this syndrome becomes clinically manifest in 95% of them. Usually patients with MEN 1 have a family relative with this disorder.  In most cases, MEN 1 is manifested by tumors of the parathyroid, pancreas and pituitary gland. The most important sign that appears in MEN1 is hyperparathyroidism, which causes disturbances of calcium in the body that can lead to kidney stones, weak bones (fractures), nausea, vomiting, hypertension, fatigue.

In MEN 1 syndrome, endocrine or non-endocrine neoplasms can develop such as thyroid, adrenal cancers, visceral and cutaneous lipomas, meningiomas, etc.. There is a great variability in terms of MEN1 phenotype. A patient who has endocrinopathies given by two of the three target endocrine glands (pancreas, pituitary, parathyroid) or endocrinopathy on one ofthe  three typical endocrine glands plus one first-degree relative with MEN1, the MEN 1 syndrome should be suspected.

Typically, tumors in MEN 1 are benign and the symptoms are due to excessive production of hormones or mass effect. However, some patients with MEN 1 have increased risk for cancer, so it is recommended cancer screening in patients with MEN.

Alzheimer’s disease may be triggered by stress hormone

According to researchers at Temple’s School of Medicine, Alzheimer’s disease may be triggered by steroids, which are hormones released by the adrenal glands in situations of stress. This could be a key trigger that underlies the mechanism of Alzheimer’s disease ( AD) with late onset.

The link between stress hormones and Alzheimer’s disease has been emphasized by previous studies that have shown that the level of corticosteroids is two to three times higher in AD patients compared to patients without AD. Domenico Pratico, professor of pharmacology and microbiology and immunology in Temple’s School of Medicine, who led the study, said that stress is an environmental factor that seem to have a role in causing Alzheimer’s disease. The explanation is that when you have elevated stress hormones for long time, they can cause neuronal cell death, which harms memory and learning. To investigate this hypothesis, Temple’s School of Medicine researchers have conducted several experiments to elucidate the mechanisms by which stress causes Alzheimer’s disease.

Alzheimer’s Disease

To perform these experiments, the researchers used triple transgenic mice that have developed the two hallmarks of Alzheimer’s disease, that is beta amyloid protein and the tau protein. One group of mice received injections with high levels of corticosteroid daily for a week to mimic stress. Researchers found no significant differences in terms of memory, but what they noticed was that tau protein was significantly increased in rats that received injections of corticosteroids. In addition, what is interesting is that the synapses, the connections between neurons, have been damaged or destroyed.

Pratico pointed out that this was surprising because they have not found memory or learning impairment although the pathology was visibly affected. The researchers also pointed out that another surprising result was that a third group of mice that were genetically engineered to lack the enzyme 5-lipoxygenase in the brain appeared to be immune and had no neurological damage from corticosteroid. Previous studies conducted by Pratico have shown that high levels of 5-lipoxygenase resulted in increasing levels of amyloid and tau protein in the brain regions responsible for memory and learning (that contribute to Alzheimer’s disease).

The conclusion was that corticosteroids use 5-lipoxygenase as a mechanism to injure synapses leading to learning and memory impairment, which are the main symptoms in AD. “So that is strong support for the hypothesis that if you block 5-lipoxygenase, you can probably block the negative effects of corticosteroid in the brain” added Pratico.

Urinary tract infection in menopause is linked to low estrogens levels

Latest studies on urinary tract infections led by researchers at Karolinska Institutet show that estrogens stimulate the production of the body’s own antibiotics and strengthens the cells to fight urinary tract infection. These findings show that post-menopausal women are more prone to recurrent urinary tract infections and that estrogen supplements might help. The study results are published in the scientific journal Science Translational Medicine.

Urinary tract infection is defined as the presence and multiplication of bacteria in the urinary tract. There are two types of urinary tract infections: infection of the lower urinary tract, which refers to cystitis, pyelocystitis, urethritis, prostatitis, and upper urinary tract infection, which refers to infection of the renal parenchyma, that is pyelonephritis, which can be acute or chronic. The most common germs that cause urinary tract infections are Gram-negative bacteria such as E. coli, Klebsiella, Proteus, Pseudomonas aeruginosa. The main factors that lead to urinary tract infection are bacterial virulence (fimbriae, lipopolysaccharide, capsular agent) and host susceptibility (urinary tract abnormalities, systemic diseases).

Urinary Tract Infection

Urinary tract infections are among the most common diseases that affect women as about half of them have at least one episode of urinary tract infection at some point in life, and 25% develop recurrences. It was found that women in post-menopause have a higher risk of recurrent urinary tract infection and this is due to low levels of estrogen. For an infection to occur, it is necessary that the bacteria come in contact with the bladder. Urinary bladder is made up of special epithelial cells that protects vulnerable tissue and produce antimicrobial peptides (which have an antibiotic-like effect).

These antimicrobial peptides are the first to act when the bladder comes in contact with bacteria. Because these peptides act very quickly, the bacteria do have time to multiply and thus no infection occurs. In contrast, in post-menopausal women, the bladder epithelium is more fragile and often damaged (which lead to gaps between cells that allow the dissemination of bacteria and infection).

In the study conducted by researchers at Karolinska Institutet, 14 post-menopausal women were given estrogen for 14 days. After treatment with estrogen, the researchers analyzed cells excreted in urine and saw that the gaps that were previously in bladder epithelium disappeared. Dr. Annelie Brauner at the Department of Microbiology, Tumor and Cell Biology, who is responsible for the study, said: “By treating post-menopausal women locally with estrogen the cells lining the bladder are strengthened and the body’s own defense against infection is improved, making women better suited to fight infections.”

An earlier treatment means a better recovery for patients with stroke

Stroke is a medical emergency and early treatment is essential for patient recovery. Therefore, bringing the patient in time, after the stroke occurs, to the emergency room for specific treatment (fibrinolysis), is crucial. But so far there have been limited information regarding how the timing of administration of tissue plasminogen activator, or tPA, influences the outcome of patients with ischemic stroke, the most common type of stroke. Now a team of researchers from the University of California, Los Angeles conducted a study on more than 50 000 stroke patients treated with tPA. They wanted to see how critical is the timing between stroke onset and treatment.

Dr. Jeffrey Saver, a professor of neurology and director of the UCLA Stroke Center, said they found that the timing of the treatment had a strong influence on recovery and that the faster the treatment was applied, the better the results. He also added the patients who receive early treatment recovers much better: “Beginning treatment earlier resulted in an improved ability to walk, the ability to remain living independently, less bleeding in the brain and reduced mortality.”

stroke

Previous studies have demonstrated that intravenous tPA up to 4.5 hours after stroke helps patients with  moderate to severe acute ischemic stroke. The data so far show that the maximum benefit comes when patients are treated very early after stroke and that it starts to decrease after 4.5 hours. But the disadvantage is that these data were drawn from a relatively small number of studies (eight studies conducted on 1,850 patients treated with tPA) and cannot be extrapolated to the general population. Therefore, the study conducted by researchers at UCLA used a large national registry to determine more accurately the association between time to treatment and stroke.

The study was conducted on a sample of 58 353 patients with acute ischemic stroke treated with tPA in the first 4.5 hours from stroke. The average patient age was 72 years and the average time from the onset of stroke to treatment was 144 minutes (about 2 hours and a half). After analyzing the medical history of the patients, the researchers were able to confirm precisely how critical is the time gap between the occurrence of stroke and receiving treatment. Saver pointed out that they knew from imaging investigations that the volume of irreversibly damaged brain tissue after ischemic stroke is expanding rapidly over time and that it takes more than 2 million neurons per minute for additional blood flow in the brain to be restored.

Lack of sleep is linked to Diabetes

Latest research on diabetes presented at The Endocrine Society’s 95th Annual Meeting in San Francisco, reveals that type II diabetes could be prevented if we got enough sleep. According to researchers at Los Angeles Biomedical Research Institute (LA BioMed), people who lose sleep during their work week could prevent the onset of this metabolic disease if they recover the those hours of sleep during weekend.

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The study, which was led by Peter Liu, MD, PhD, lead researcher at BioMed, shows that insulin sensitivity significantly improves after three nights of catch-up sleep on weekends. Recovering the body after sleep restriction during the week and lead to better insulin sensitivity and this lowers the risk of type II diabetes. Liu said that reducing the incidence of this chronic metabolic diseases is critical in a nation where diabetes affects 26 million people and the costs are huge (about $ 174 million annually).

sleep

Insulin is a hormone produced by the pancreas and regulates blood glucose. Insulin helps the glucose to enter the cells after we eat, in order to be used as a source of energy. When glucose remains in the blood, hyperglycemia occurs, which is characteristic of diabetes. Diabetes can occur either when the pancreas does not produce enough insulin or when the body loses sensitivity to insulin (hyperglycemia occurs in both cases). In type II diabetes, the body becomes resistant to insulin, which means that the pancreas produces the hormone but it cannot be used properly. If the body recovers insulin sensitivity, type II diabetes could be avoided.

Studies on the link between sleep and diabetes have already been made and have shown that in  healthy, normal sleepers sleep restriction can have harmful effects. New study investigates the profile of men who sleep less during the week because of their job, but recover those lost hours of sleep during the weekend.

The study was conducted on a sample of 19 men (average age 28 years) who stated that they had inadequate sleep for six months or more. On average each man had about six hours of sleep per night. But those hours lost were recovered over the weekend when they slept an extra 37.4 percent, or 2.3 hours, per night. After several experiments in the laboratory, the researchers measured the levels of glucose and insulin and then insulin sensitivity was calculated. It was found that insulin sensitivity was better in men who slept 10 hours a night on each of three nights of catch-up sleep than when they had slept restriction.