Scientists find link between congenital cardiac malformation and adult adrenal cancer

An international team  discovered a genetic mutation that explains why adults with severe congenital heart defects—who live with low oxygen in their blood—are at dramatically high risk for adrenal gland cancer.
 
The study focused on patients who were born with cyanotic congenital heart disease and went on to develop adrenal gland or related tumors called pheochromocytomas or paragangliomas. Detailed genetic analysis of these cases revealed mutations in a gene that regulates a hypoxia (low oxygen)-related pathway called EPAS1, also known as HIF2A. Cyanotic refers to a bluish or purplish discoloration that occurs when blood levels of oxygen are low. Patients with cyanotic heart disease have a sixfold higher risk of developing the adrenal gland tumors than patients without this severe type of heart disease, but the genetic basis for this heightened incidence was unknown.

An amplified response
"It was suspected that in patients with cyanotic heart disease, the low oxygen levels might lead directly to the growth of pheochromocytomas," said a professor of medicine. "We found instead that a genetic mutation is the main reason why the tumor can appear in these patients. Most remarkably, the mutation turns on the main gene that causes the body to respond to low oxygen, further amplifying this response."

"This finding provides important insights into our understanding of how the body adapts to conditions of low oxygen and how this can lead to tumors," said  the Dr.

A perfect storm
"We found that this mutation is not inherited but is acquired later," the Dr. said. "The patient's heart  disease may create conditions that make it more likely for the mutation to appear. Understanding this mechanism requires further studies."

Importantly, clinical-grade inhibitors of HIF2A exist and are in early clinical trials for a variety of conditions, including pheochromocytomas. "Thus, this discovery can potentially have an impact on patients' lives," the  Dr. said. 

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Heavy periods may soon be a thing of the past

Women who suffer from heavy periods can attest how terrible it feels when their time of the month comes around. Thankfully, heavy periods may soon be a thing of the past thanks to a pioneering new study into the causes of heavy menstrual bleeding, according to a report.
 
Researchers explored how the shedding of the endometrium (the womb lining) is linked to dropping levels of oxygen during menstruation.

When the endometrium is shed, this causes a woman to bleed during her period.

In order to reduce the amount of blood lost, the surface of the womb that has lost its lining must heal.

The study, which was published , noted that when hypoxia occurred (lowered levels of oxygen), the body produced a protein called HIF-1 (hypoxia inducible factor one).

Production of the HIF-1 protein speeds up the healing process of the womb lining.

The researchers realised that women with heavy periods typically had lower levels of HIF-1 in comparison to women with a lighter flow.

Therefore, creating a treatment for women with heavy periods that boosts their levels of HIF-1 could be the key to helping millions of women worldwide.

A clinical lecturer in obstetrics and gynaecology and leader of the study, explained the significance of the team’s breakthrough. 

“Our findings reveal for the first time that HIF-1 and reduced levels of oxygen in the womb are required during a period to optimise repair of the womb lining,” she said.

“Excitingly, increasing levels of the HIF-1 protein in mice shows real promise as a novel, non-hormonal medical treatment.”

“Heavy bleeding is a debilitating and common condition that affects thousands of women and girls but too often gets dismissed,” she said.

“These findings give hope to women who have suffered in silence with the condition for too long.”

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.    

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Signs And Symptoms of COPD And How to Manage

What Are the Signs and Symptoms of COPD?

At first, COPD may cause no symptoms or only mild symptoms. As the disease gets worse, symptoms usually become more severe. Common signs and symptoms of COPD include:

• An ongoing cough or a cough that produces a lot of mucus (often called "smoker's cough")
• Shortness of breath, especially with physical activity
• Wheezing (a whistling or squeaky sound when you breathe)
• Chest tightness

If you have COPD, you also may have colds or the flu (influenza) often.

Not everyone who has the symptoms above has COPD. Likewise, not everyone who has COPD has these symptoms. Some of the symptoms of COPD are similar to the symptoms of other diseases and conditions. Your doctor can find out whether you have COPD.

If your symptoms are mild, you may not notice them, or you may adjust your lifestyle to make breathing easier. For example, you may take the elevator instead of the stairs.

Over time, symptoms may become severe enough to see a doctor. For example, you may get short of breath during physical exertion.

The severity of your symptoms will depend on how much lung damage you have. If you keep smoking, the damage will occur faster than if you stop smoking.

Severe COPD can cause other symptoms, such as swelling in your ankles, feet, or legs; weight loss; and lower muscle endurance.

Some severe symptoms may require treatment in a hospital. You—with the help of family members or friends, if you're unable—should seek emergency care if:

• You're having a hard time catching your breath or talking.
• Your lips or fingernails turn blue or gray. (This is a sign of a low oxygen level in your blood.)
• You're not mentally alert.
• Your heartbeat is very fast.
• The recommended treatment for symptoms that are getting worse isn't working.

Management of COPD

• Do activities slowly.
• Put items that you need often in one place that's easy to reach.
• Find very simple ways to cook, clean, and do other chores. For example, you might want to use a small table or cart with wheels to move things around and a pole or tongs with long handles to reach things.
• Ask for help moving things around in your house so that you won't need to climb stairs as often.
• Keep your clothes loose, and wear clothes and shoes that are easy to put on and take off.

Depending on how severe your disease is, you may want to ask your family and friends for help with daily tasks.

Prepare for Emergencies

If you have COPD, know when and where to seek help for your symptoms. You should get emergency care if you have severe symptoms, such as trouble catching your breath or talking. 

Call your doctor if you notice that your symptoms are worsening or if you have signs of an infection, such as a fever. Your doctor may change or adjust your treatments to relieve and treat symptoms.

Keep phone numbers handy for your doctor, hospital, and someone who can take you for medical care. You also should have on hand directions to the doctor's office and hospital and a list of all the medicines you're taking.

Emotional Issues and Support

Living with COPD may cause fear, anxiety, depression, and stress. Talk about how you feel with your health care team. Talking to a professional counselor also might help. If you're very depressed, your doctor may recommend medicines or other treatments that can improve your quality of life.

Joining a patient support group may help you adjust to living with COPD. You can see how other people who have the same symptoms have coped with them. Talk with your doctor about local support groups or check with an area medical center.

Support from family and friends also can help relieve stress and anxiety. Let your loved ones know how you feel and what they can do to help you.

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Why we suffer from chronic mountain sickness

Researchers have decoded the genetic basis of chronic mountain sickness (CMS) or Monge's disease.

Their study provides important information that validates the genetic basis of adaptation to high altitudes, and provides potential targets for CMS treatment.

More than 140 million people have permanently settled on high-altitude regions, on continents ranging from African and Asia to South America. The low-oxygen conditions at such high altitudes present a challenge for survival, and these geographically distinct populations have adapted to cope with hypoxia, or low levels of oxygen in the blood.

Interestingly, many humans living at high elevations, particularly in the Andes mountain region of South America, are maladapted and suffer CMS. The disease is characterized by an array of neurologic symptoms, including headache, fatigue, sleepiness and depression.

Often, people with CMS suffer from strokes or heart attacks in early adulthood because of increased blood viscosity (resistance to blood flow that can result in decreased oxygen delivery to organs and tissues).

Past studies of various populations show that CMS is common in Andeans, occasionally found in Tibetans and absent from Ethiopians living on the East African high-altitude plateau.

Therefore, the researchers dissected the genetic mechanisms underlying high-altitude adaptation by comparing genetic variation between Peruvian individuals from the Andes region with CMS and adapted subjects without CMS, using whole genome sequencing.

They identified two genes, ANP32D and SENP1, with significantly increased expression in the CMS individuals when compared to the non-CMS individuals, and hypothesized that down-regulating these genes could be beneficial in coping with hypoxia.

Aresearcher said that while a number of published articles have described an association between certain genes and the ability for humans to withstand low oxygen at high levels, it was very hard to be sure if the association was causal.

The researchers therefore looked at genetic orthologs - corresponding gene sequences from another species, in this case the fruit fly - to assess the impact of observed genetic changes on function under conditions of hypoxia.

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Low oxygen levels drive cancer growth'

Low oxygen levels in cells, not genetic mutations, may fuel uncontrollable cancer growth, says a new discovery.

If hypoxia, or low oxygen levels in cells, is proven to be a key driver of certain types of cancer, treatment plans for curing the malignant growth can change in significant ways, said Ying Xu, professor of bioinformatics and computational biology at Georgia University's Franklin College of Arts and Sciences.

The research team analysed samples of messenger RNA data, also called transcriptomic data, from seven different cancer types in a publicly available database.

They found that long-term lack of oxygen in cells may be a key driver of cancer growth, the Journal of Molecular Cell Biology reports.

Previous studies had linked low oxygen levels in cells as a contributing factor in cancer development, but not as the driving force for cancer growth.

High cancer rates worldwide cannot be explained by chance genetic mutations alone, Xu said, according to a Georgia statement.

He added that bioinformatics, which melds biology and computational science, has allowed researchers to see cancer in a new light.

"Cancer drugs try to get to the root, at the molecular level, of a particular mutation, but the cancer often bypasses it," Xu said.

"So we think that possibly, genetic mutations may not be the main driver of cancer."

The researchers analysed data downloaded from the Stanford Microarray database via a software programme to detect abnormal gene expression patterns in seven cancers: breast, kidney, liver, lung, ovary, pancreatic and stomach.

Xu relied on the gene HIF1A as a biomarker of the amount of molecular oxygen in a cell. All seven cancers showed increasing amounts of HIF1A, indicating decreasing oxygen levels in the cancer cells.

Low oxygen levels in a cell interrupt the activity of oxidative phosphorylation, a term for the highly efficient way that cells normally use to convert food to energy.

Low oxygen levels engender the process of creating new blood vessels. They provide fresh oxygen, thus improving oxygen levels in the cell and tumour and slowing the cancer growth — but only temporarily.

"When a cancer cell gets more food, it grows; this makes the tumour biomass bigger and even more hypoxic. In turn, the energy-conversion efficiency goes further down, making the cells even hungrier and triggering the cells to get more food from blood circulation, creating a vicious cycle. This could be a key driver of cancer," Xu said.