Friday, August 9, 2019

Researchers identify a possible therapeutic target for Kennedy's disease and prostate cancer


NEWS RELEASE 8-AUG-2019

Researchers identify a possible therapeutic target for Kennedy's disease and prostate cancer


INSTITUTE FOR RESEARCH IN BIOMEDICINE (IRB BARCELONA)


A study led by scientists at the Institute for Research in Biomedicine (IRB Barcelona) and published in Nature Communicationsproposes chaperone protein Hps70 as an attractive therapeutic target for the treatment of Kennedy's disease--a rare neuromuscular condition--and of castration-resistant prostate cancer.

Kennedy´s disease is caused by a mutation in the androgen receptor. This receptor serves as a sensor of testosterone, detecting the levels of this hormone and activating the genes responsible for male traits. But in patients with this disease, the mutated receptor shows an altered structure, as demonstrated by this lab in a previous study recently published in the same journal, and it forms aggregates that damage muscle cells and causes muscular atrophy or wasting.

Chaperone proteins are one of the mechanisms through which the formation of toxic protein aggregates is prevented. These chaperones bind to other proteins in order to facilitate their correct folding, assembly and transport, as well as regulating their degradation. "But we didn't know the role of these chaperones in the regulation of the activity, cell concentration and solubility of the androgen receptor," says ICREA researcher Xavier Salvatella, head of the Laboratory of Molecular Biophysics at IRB Barcelona.

Using a sophisticated biophysics approach, nuclear magnetic resonance (NMR), and experiments with human cell cultures, the scientists discovered that the chaperones Hsp40 and Hsp70 bind strongly to a region of the androgen receptor that is susceptible to forming toxic aggregates. This interaction between the chaperones and the receptor prevents the formation of these deposits and facilitates their clearance.

To confirm whether the increase in the activity of these chaperones decreases the formation of toxic aggregates and whether these proteins are therefore useful for the treatment of Kennedy`s disease, the scientists performed experiments in mouse models. These experiments were done in collaboration with the labs of Professors Jason E. Gestwicki and Andrew P. Lieberman from the University of California San Francisco and the University of Michigan, respectively.

"The results obtain in mice confirm that compounds that activate Hsp70 lead to a decrease in the formation of the aggregates," says Salvatella. "Therefore the chaperone Hsp70 emerges as a possible therapeutic target for Kennedy's disease," he goes on to say.

The results may also be useful in the search for a treatment for castration-resistant prostate cancer, the most advanced stage of this kind of cancer, which causes 30,000 deaths a year in Europe. In cells resistant to current treatments, the binding site of Hsp40 and Hsp70 in the androgen receptor is not altered, and therefore these chaperones may also serve as a therapeutic target in this disease.

Friday, August 2, 2019

Excessive Phlegm Buildup

It seems my Kennedy's Disease always finds new ways to intrude on my life. Excessive amounts of phlegm have become an almost daily ordeal for me. Here are two techniques to help clear your lungs plus an article on potential home remedies. 
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How to Perform a Controlled Cough

Not all coughs are created equal though. Explosive, uncontrolled hacking does little to clear airways. In fact, a violent cough can cause the airways to collapse, making it even more difficult to clear them of mucus.

An effective cough is one that's controlled and that comes from deep within the lungs to loosen and mobilize mucus. It's something you can easily learn to do with practice. And once you've mastered the technique, you can call on it whenever you need it. 

  1. Sit upright in a chair or on the edge of a bed. Place your feet firmly on the ground, lean forward a bit, and take a few deep breaths to help your body to relax. 
  2. Fold both arms across your abdomen and breathe in fully through your nose.  
  3. As you exhale, lean forward a little more and press your arms against your abdomen. Open your mouth slightly and cough two or three times. Each cough should be short and sharp and you should feel your diaphragm move upward. 
  4. Breathe in slowly by gently sniffing throughout the entire inhalation. This will prevent mucus from being pushed back into the airways. 
  5. Rest and repeat if necessary. 

You may want to cough into a tissue and note the color, thickness, or overall appearance of what you bring up. If you notice any significant changes, let your doctor know.

To get the best from controlled coughing, incorporate these simple tips:

  1. Stay hydrated. Sticky mucus can be difficult to cough up. To help keep it thin and easy to expectorate, drink plenty of water throughout the day—at least six to eight glasses.
  2. Use a bronchodilator before you do controlled coughing. This will relax your airways to allow mucus to move more easily. ted, mucus clearance is more difficult.
  3. Slow down your breathing. After coughing, keep your breaths slow and shallow. If you inhale sharply and quickly it can interfere with the movement of mucus out of the lungs—precisely the effect you want to avoid.
Source:  https://www.verywellhealth.com/coughing-as-an-airway-clearance-technique-914980
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Chest Percussion

An Airway Clearance Technique to Ease Mucous Blockage

Chest percussion is used frequently to help you clear your airways.

It literally involves "percussion" on your chest and/or back—in other words, your partner or a healthcare worker will clap you on your chest or back to help loosen the thick mucus in your lungs. Chest percussion also can be performed using electronic devices or other instruments that vibrate your chest.

When you loosen mucus using chest percussion, it will help you to cough it up.

Chest percussion is considered a part of chest physical therapy. The overall goal of chest physical therapy is to make it easier for you to expel mucus in your airways, which in turn should make it easier for you to breathe.

Performing Chest Percussion


Your doctor or respiratory therapist will give you specific instructions on how to perform chest percussion. You should always follow the instructions of your healthcare team, but here are some general guidelines on how the procedure normally is performed.

You'll likely be instructed to perform chest percussion at least once per day in several different positions: seated, on your back with a pillow under your chest so that your head tilts downward, and on your stomach, again with your head tilted downward.

If you're using a mechanical airway clearance device for your chest percussion, your doctor will show you how to use the device.

If you're doing the procedure manually, your partner (or a healthcare worker) will then clap you on the back or the chest (whichever is exposed) with their hand, quickly and repeatedly.

It's important to use the correct hand position to perform manual chest percussion: the person's hand should be in a cupped position, with fingers and thumb together. It's also important to clap on the sides of the chest and the back, not in the middle—your physician can show you exactly where.

Finally, you shouldn't perform the procedure on bare skin—make sure you're wearing a shirt, or use a towel to cover the area to be clapped upon.

When to Perform the Procedure


The best time to perform chest percussion is in the morning since it's likely that your lungs will have built up mucus during the night. If you have a problem with coughing overnight, you can consider performing it right before you go to bed, as well.

Of course, your doctor will advise you on the best times to perform the procedure. Chest percussion works best after a bronchodilator treatment, so you might want to keep that in mind.

It's not a good idea, though, to perform chest percussion right after you've eaten—banging on your chest or back following even a small meal could make you sick.

Another tidbit is that you should combine chest percussion with coughing or with other methods to bring up the mucus that is loosened by your efforts. 

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Home remedies for mucus in the chest


A person can soothe symptoms and get rid of bothersome mucus using the following methods:

1. Warm fluids

Hot beverages can provide immediate and sustained relief from a mucus buildup in the chest.

Staying hydrated thins mucus, making it easier to expel by coughing.

According to a 2008 study, hot beverages provide "immediate and sustained relief" from congestion and accompanying symptoms, such as sneezing, a nagging cough, a sore throat, and chills.

A person can benefit from drinking:
  • broths
  • decaffeinated black or green tea
  • herbal teas
  • warm water

Some of these drinks are available for purchase online, including decaffeinated tea and herbal teas.

2. Steam

Keeping the air moist can loosen mucus and reduce congestion and coughing. The National Heart, Lung, and Blood Institute recommend using a cool-mist humidifier or steam vaporizer.

People with difficulty sleeping may wish to use a humidifier at night. To maximize the effects, keep windows and doors closed.

Humidifiers must be cleaned regularly to remove bacteria and other pathogens that can make symptoms worse and lead to infection.

Other ways to increase moisture in the air include:

Inhaling steam: Fill a large bowl with hot water. Lean over the bowl and drape a towel over the head to contain the stream. Gently inhale the steam to loosen mucus.
Having a hot shower or bath: The hot water will fill the room with steam and help to alleviate symptoms.

Breathe in the steam for as long as is comfortable, then drink a glass of water to prevent dehydration.

3. Saltwater

Gargling with a mixture of salt and warm water can remove phlegm and mucus from the back of the throat and ease symptoms.

Add half a teaspoon of salt to a cup of warm water. Stir until the salt dissolves.

Gargle with the mixture and allow it to sit in the back of the throat momentarily. Repeat several times a day as needed.

4. Honey


Honey is a popular home remedy, and research suggests that it has antiviral and antibacterial properties.

A person can consume 1 tablespoon of honey every 3 to 4 hours, until the symptoms ease. Honey is not suitable for infants under 12 months of age. 

5. Foods and herbs

Foods most commonly used to alleviate coughs, colds, and a buildup of mucus include:
garlic
ginger
lemon