Aspirin , parasites and liver cancer

A study showed that aspirin significantly inhibited the PGHS activity as well as the motility of mf and adult parasites [5]. Aspirin, a nonsteroidal anti-inflammatory drug (NSAID) used basically to decrease pain and inflammation. However, the mode of action by which aspirin kills the parasite was not known.

Data from the study show that taking aspirinon a regular basis can lower the risk of developing liver cancer, or hepatocellular carcinoma (HCC).

The scientists defined “a regular basis” as taking two or more 325-milligram tablets per week for 5 years or more.

The study’s results are promising. “Regular use of aspirin led to significantly lower risk of developing HCC, compared to infrequent or no aspirin use, and we also found that the risk declined progressively with increasing aspirin dose and duration of use,” says lead author Dr. Tracey Simon, who is a research fellow from the Massachusetts General Hospital Division of Gastroenterology in Boston.

Heavy or long-term use of some of these medicines, such as ibuprofen, naproxen, and higher dose aspirin, can cause chronic kidney disease known as chronic interstitial nephritis. … If you have decreased kidney function, painkillers called NSAIDs (see below) and higher dose aspirin are not recommended.

In August 2014 scientists published an analysis of previous aspirin studies. The study confirmed that aspirin can lower the risk of developing bowel, stomach and oesophageal cancers. It can also lower the risk of lung, prostate and breast cancersbut not as much as the other cancer types.

Aspirin Linked to Lower Brain Cancer Risk. In the study, researchers found that people who regularly took aspirin had a nearly 34 percent lower risk of a type of brain tumor called a glioma, compared with people who didn’t take aspirin regularly.

Lymphatic fluid is squeezed through the vessels when we use our muscles

Lymphatic system is part of the immune system

  •  maintains fluid balance and plays a role in absorbing fats and fat-soluble nutrients
  • involves an extensive network of vessels that passes through almost all our tissues to allow for the movement of a fluid called lymph
  • lymph circulates through the body in a similar way to blood
How do you keep the lymph system healthy?
  1. Regular exercise
    can help to reduce the amount of tissue edema and swelling that the veins and lymph system need to clear.
  2. Treat lymph system damage early.  If you have swelling in an arm or leg from previous injury or cancer treatment, make sure you get treatment early. Reducing the length of time that the lymph system is over-taxed may decrease the long term damage. Kind of like a hernia – you should get it fixed sooner rather than later or it will just expand and get worse.
  3. Avoid tight fitting clothes.  If you have lymphatic issues, compressing the area with tight clothing will only make things worse.
  4. Physical therapy.  Some physical therapists (PTs) specialize in treating lymphedema. They have developed excellent massage techniques that can help to “milk” the lymph back to the blood circulation (called manual lymph drainage). They can also provide special wraps to reduce arm and leg swelling.

Lymphatic filariasis is a parasitic disease caused by three species of microscopic, thread-like worms. The adult worms only live in the human lymph system. The lymph system maintains the body’s fluid balance and fights infections. … People with theworms in their blood can give the infection to others through mosquitoes.

The filarial parasites specifically target the lymphatics and impair lymph flow, which is critical for the normal functions of the lymphatic system

Note: Women should not wear tight fitting clothes to allow the lymph to function and clean the blood.

LYMPHATIC CIRCULATION

The lymph is moved through the body in its own vessels making a one-way journey from the interstitial spaces to the subclavian veins at the base of the neck.

  • Since the lymphatic system does not have a heart to pump it, its upward movement depends on the motions of the muscle and joint pumps.
  • As it moves upward toward the neck the lymph passes through lymph nodes which filter it  to remove debris and pathogens.
  • The cleansed lymph continues to travel in only one direction, which is upward toward the neck.
  • At the base of the neck, the cleansed lymph flows into the subclavian veins on either side of the neck.

What can go wrong with the lymphatic system?

  1. Mechanical damage can disrupt the flow of lymph fluid, causing fluid back up and swelling.
    The lymph vessels are very delicate (almost like spider webs), and their walls are not as tough as arteries or veins. They are therefore quite prone to injury by mechanical and compressive forces. The most common causes of lymphatic system injury are surgery, radiation, and trauma. Luckily the lymphatic system is a complex web that can usually find flow work-arounds. However, if there is extensive damage in a specific area, it can be overwhelming and result in swelling to the nearby limb (for example) previously served by that part of the system.
  2. Cancer can plug up the system or cancer treatment can damage the lymphatics.
    When white blood cells divide out of control and become cancerous, it makes sense that they can damage the circulatory lymph system where they live. Lymphoma is a cancer of the lymph system that directly damages it. Sometimes cancer spreads through the lymph system and travels to other parts of the body. When cancer gets into the lymph nodes, physicians sometimes have to cut those nodes out (lymph node dissections are common in breast cancer treatment, for example) or use radiation to burn the cancer. This can lead to chronic swelling issues in the arms or legs, known as lymphedema.
  3. Parasites can block the lymphatic system.
    As discussed earlier, certain parasitic worms have an affinity for the lymph system and although they can be killed with medicines, the damage they do to the lymph vessels and nodes may be permanent.

There are about 600 lymph nodes in the body. These nodes swell in response to infection, due to a build-up of lymph fluid, bacteria, or other organisms and immune system cells.

A person with a throat infection, for example, may feel that their “glands” are swollen. Swollen glands can be felt especially under the jaw, in the armpits, or in the groin area. These are, in fact, not glands but lymph nodes.

They should see a doctor if swelling does not go away, if nodes are hard or rubbery and difficult to move, if there is a fever, unexplained weight-loss, or difficulty breathing or swallowing.

Source: https://www.medicalnewstoday.com/articles/303087.php

Fast facts about the lymphatic system

  • The lymphatic system plays a key role in the immune system, fluid balance, and absorption of fats and fat-soluble nutrients.
  • As lymph vessels drain fluid from body tissues, this enables foreign material to be delivered to the lymph nodes for assessment by immune system cells.
  • The lymph nodes swell in response to infection, due to a build-up of lymph fluid, bacteria, or other organisms and immune system cells.
  • Lymph nodes can also become infected, in a condition known as lymphadenitis.
  • If lymph nodes remain swollen, if they are hard and rubbery, and if there are other symptoms, you should see a doctor.

Definition

Lymph nodes, or

Lymph nodes, or “glands” may swell as the body responds to a threat.

The lymphatic system has three main functions:

  • It maintains the balance of fluid between the blood and tissues, known as fluid homeostasis.
  • It forms part of the body’s immune system and helps defend against bacteria and other intruders.
  • It facilitates absorption of fats and fat-soluble nutrients in the digestive system.

The system has special small vessels called lacteals. These enable it to absorb fats and fat-soluble nutrients from the gut.

They work with the blood capillaries in the folded surface membrane of the small intestine. The blood capillaries absorb other nutrients directly into the bloodstream.

Anatomy

The lymphatic system consists of lymph vessels, ducts, nodes, and other tissues.

Around 2 liters of fluid leak from the cardiovascular system into body tissues every day. The lymphatic system is a network of vessels that collect these fluids, or lymph. Lymph is a clear fluid that is derived from blood plasma.

The lymph vessels form a network of branches that reach most of the body’s tissues. They work in a similar way to the blood vessels. The lymph vessels work with the veins to return fluid from the tissues.

Unlike blood, the lymphatic fluid is not pumped but squeezed through the vessels when we use our muscles. The properties of the lymph vessel walls and the valves help control the movement of lymph. However, like veins, lymphatic vessels have valves inside them to stop fluid from flowing back in the wrong direction.

Lymph is drained progressively towards larger vessels until it reaches the two main channels, the lymphatic ducts in our trunk. From there, the filtered lymph fluid returns to the blood in the veins.

The vessels branch through junctions called lymph nodes. These are often referred to as glands, but they are not true glands as they do not form part of the endocrine system.

In the lymph nodes, immune cells assess for foreign material, such as bacteria, viruses, or fungus.

Lymph nodes are not the only lymphatic tissues in the body. The tonsils, spleen, and thymus gland are also lymphatic tissues.

What do the tonsils do?

In the back of the mouth, there are tonsils. These produce lymphocytes, a type of white blood cell, and antibodies.

They have a strategic position, hanging down from a ring forming the junction between the mouth and pharynx. This enables them to protect against inhaled and swallowed foreign bodies. The tonsils are the tissues affected by tonsillitis.

What is the spleen?

The spleen is not connected to the lymphatic system in the same way as lymph nodes, but it is lymphoid tissue. This means it plays a role in the production of white blood cells that form part of the immune system.

Its other major role is to filter the blood to remove microbes and old and damaged red blood cells and platelets.

The thymus gland

The thymus gland is a lymphatic organ and an endocrine gland that is found just behind the sternum. It secretes hormones and is crucial in the production, maturation, and differentiation of immune T cells.

It is active in developing the immune system from before birth and through childhood.

The bone marrow

Bone marrow is not lymphatic tissue, but it can be considered part of the lymphatic system because it is here that the B cell lymphocytes of the immune system mature.

Liver of a fetus

During gestation, the liver of a fetus is regarded as part of the lymphatic system as it plays a role in lymphocyte development.

Below is a 3-D model of the lymphatic system, which is fully interactive.

Explore the model using your mouse pad or touchscreen to understand more about the lymphatic system.

Function

The lymph system has three main functions.

Fluid balance

The lymphatic system helps maintain fluid balance. It returns excess fluid and proteins from the tissues that cannot be returned through the blood vessels.

The fluid is found in tissue spaces and cavities, in the tiny spaces surrounding cells, known as the interstitial spaces. These are reached by the smallest blood and lymph capillaries.

Around 90 percent of the plasma that reaches tissues from the arterial blood capillaries is returned by the venous capillaries and back along veins. The remaining 10 percent is drained back by the lymphatics.

Each day, around 2-3 liters is returned. This fluid includes proteins that are too large to be transported via the blood vessels.

Loss of the lymphatic system would be fatal within a day. Without the lymphatic system draining excess fluid, our tissues would swell, blood volume would be lost and pressure would increase.

Absorption

Most of the fats absorbed from the gastrointestinal tract are taken up in a part of the gut membrane in the small intestine that is specially adapted by the lymphatic system.

The lymphatic system has tiny lacteals in this part of the intestine that form part of the villi. These finger-like protruding structures are produced by the tiny folds in the absorptive surface of the gut.

Lacteals absorb fats and fat-soluble vitamins to form a milky white fluid called chyle.

This fluid contains lymph and emulsified fats, or free fatty acids. It delivers nutrients indirectly when it reaches the venous blood circulation. Blood capillaries take up other nutrients directly.

The immune system

The lymphatic system produces white blood cells, or lymphocytes that are crucial in fending off infections.

The lymphatic system produces white blood cells, or lymphocytes that are crucial in fending off infections.

The third function is to defend the body against unwanted organisms. Without it, we would die very soon from an infection.

Our bodies are constantly exposed to potentially hazardous micro-organisms, such as infections.

The body’s first line of defense involves:

  • physical barriers, such as the skin
  • toxic barriers, such as the acidic contents of the stomach
  • “friendly” bacteria in the body

However, pathogens often do succeed in entering the body despite these defenses. In this case, the lymphatic system enables our immune system to respond appropriately.

If the immune system is not able to fight off these micro-organisms, or pathogens, they can be harmful and even fatal.

A number of different immune cells and special molecules work together to fight off the unwanted pathogens.

How does the lymphatic system fight infection?

The lymphatic system produces white blood cells, known as lymphocytes. There are two types of lymphocyte, T cells and B cells. They both travel through the lymphatic system.

As they reach the lymph nodes, they are filtered and become activated by contact with viruses, bacteria, foreign particles, and so on in the lymph fluid. From this stage, the pathogens, or invaders, are known as antigens.

As the lymphocytes become activated, they form antibodies and start to defend the body. They can also produce antibodies from memory if they have already encountered the specific pathogen in the past.

Collections of lymph nodes are concentrated in the neck, armpits, and groin. We become aware of these on one or both sides of the neck when we develop so-called “swollen glands” in response to an illness.

It is in the lymph nodes that the lymphocytes first encounter the pathogens, communicate with each other, and set off their defensive response.

Activated lymphocytes then pass further up the lymphatic system so that they can reach the bloodstream. Now, they are equipped to spread the immune response throughout the body, through the blood circulation.

The lymphatic system and the action of lymphocytes, of which the body has trillions, form part of what immunologists call the “adaptive immune response.” These are highly specific and long-lasting responses to particular pathogens.

Diseases

The lymphatic system can stop working properly if nodes, ducts, vessels, or lymph tissues become blocked, infected, inflamed, or cancerous.

Lymphoma

Cancer that starts in the lymphatic system is known as lymphoma. It is the most serious lymphatic disease.

Hodgkin lymphoma affects a specific type of white blood cell known as Reed-Sternberg cells. Non-Hodgkin lymphoma refers to types that do not involve these cells.

Cancer that affects the lymphatic system is usually a secondary cancer. This means it has spread from a primary tumor, such as the breast, to nearby or regional lymph nodes.

Drainage areas

  • Damage disturbs the flow. When lymphatic tissues or lymph nodes have been damaged, destroyed or removed, lymph cannot drain normally from the affected area. When this happens excess lymph accumulates and results in the swelling that is characteristic of lymphedema.
  • Drainage areas. The treatment of lymphedema is based on the natural structures and the flow of lymph. The affected drainage area determines the pattern of the manual lymph drainage (MLD) and for self-massage. Although lymph does not normally cross from one area to another, MLD stimulates the flow from one area to another. It also encourages the formation of new lymph drainage pathways.
  • MLD treatment and self-massage begin by stimulating the area near the terminus and the larger lymphatic vessels. This stimulates the flow of lymph that is already in the system and frees space for the flow of the lymph that is going to enter the capillaries during the treatment.
  • MLD treatment continues as a gentle massage technique to stimulate the movement of the excess lymph in affected tissues. The rhythmic, light strokes of MLD provide just the right pressure to encourage this excess lymph to flow into the lymph capillaries.
  • The compression garments, aids, and/or bandages that are worn between treatments help control swelling by providing pressure that is needed to encourage the flow of lymph into the capillaries.
  • Exercise is important in the treatment of lymphedema because the movements of the muscles stimulate the flow of the lymph into the capillaries. Wearing a compression garment during exercise also provides resistance to further stimulate this flow.
  • Self-massage or simplified lympatic drainage, as prescribed by your therapist, is another way in which lymph is encouraged to flow into the capillaries. Each self-massage session begins at the terminus with strokes to stimulate the flow of lymph that is already in the system. This is followed by specialized strokes that encourage the flow of lymph into the capillaries and then upward to the terminus.

Other lymphatic system organs

The lymphatic system includes other organs, such as the spleen, thymus, tonsils and adenoids.

The spleen

The spleen is under your ribs, on the left side of your body. It has 2 main different types of tissue, red pulp and white pulp.

The red pulp filters worn out and damaged red blood cells from the blood and recycles them.

The white pulp contains many B lymphocytes and T lymphocytes. These are white blood cells that are very important for fighting infection. As blood passes through the spleen, these blood cells pick up on any sign of infection or illness and begin to fight it.

The thymus

The thymus is a small gland under your breast bone. It helps to produce white blood cells to fight infection. It is usually most active in teenagers and shrinks in adulthood.

The tonsils and adenoids

The tonsils are 2 glands in the back of your throat.

The adenoids are glands at the back of your nose, where it meets the back of your throat. The adenoids are also called the nasopharyngeal tonsils.

The tonsils and adenoids help to protect the entrance to the digestive system and the lungs from bacteria and viruses.

Exercises

https://www.google.com/search?q=exercises+for+the+lymphatic+system&rlz=1CAVNXA_enUS848&oq=exercises+for+the+lypm&aqs=chrome.1.69i57j0.8284j0j7&sourceid=chrome&ie=UTF-8

Massage

https://www.google.com/search?rlz=1CAVNXA_enUS848&ei=wu44XaKIMM680PEP3NissAE&q=massage+lymphatic+nodes&oq=massage+lymphatic+nodes&gs_l=psy-ab.3..0i22i30l10.4545.6438..6659…0.0..0.118.705.7j1……0….1..gws-wiz…….0i71j0i13j0i13i30j0.7JrbPFXh7KI&ved=0ahUKEwii8c7J387jAhVOHjQIHVwsCxYQ4dUDCAo&uact=5

 

Anti-parasitic and anti Covid19 diet by Connie

Up to nearly 10% of Americans may be infected with brain parasites found in undercooked meat. One example is the brain-invasive pork tapeworm, which is the most common cause of adult-onset epilepsy. Allergenic fish worms found in nearly two-thirds of retail fish tested can trigger allergic reactions in sensitive individuals. There have been migratory skin worms found in undercooked fish (like in sushi). Cheese may contain mites and maggots and organ meats may contain other worms.

Cheese: asiago, bel paese, bleu/blue, brick, brie, camembert, emmental, gorgonzola, gruyere, muenster, port de salut, roquefort, stilton, swiss, pork

Nearly 95% of tested retail U.S. beef (including burgers) has been found to be parasite infested. The meat industry has responded to this problem by feeding arsenic to chickens and turkeys to reduce the parasite load; this arsenic may be linked to increased cancer risk in consumers, and adding bacteria-eating viruses to meat would not help one avoid the brain parasite, toxoplasma, the second leading cause of foodborne disease-related death in the United States. Being bitten by the external parasite, a lone star tick, may result in developing an allergy to meat.

Anti-parasitic diet by Connie Dello Buono

  • Avoid cheese, under-cooked meat, salads and produce not properly washed with vinegar or salt water, over ripe fruits, eat limes and berries, pineapple and papaya, sweet potatoes or yams, pine nuts, and eat less on fermented foods (except fiber-rich).
  • Consume less fat and sugar filled and processed foods but eat more fiber-rich foods, freshly cooked and well cooked. Combine meat with veggies. Eat less fermented veggies and alcohol drinks.
  • Add cabbage , tomatoes and lemon when cooking fish or meat to kill the parasites.  Boil milk if you wanted to drink 2% milk.  Add garlic, onions and sulfur rich foods in your meals daily. Eat well washed raw carrots and garlic.
  • Have a banana at night (not over ripe).
  • Avoid caffeine and chocolate until you have completed your anti-parasitic meds.
  • Lowering your fat intake from keto diet, lowers the supply of cholesterol for parasites to thrive.
  • Warm drink of decaf tea, soy milk, almond milk
  • Use all kinds of coconut from oil to milk.  Do not consume 3-day old rice or left over foods. Wear gloves when washing fish.
  • Promote good hygiene. Freeze fish for portion you cannot eat within 2 days.  Do not eat wilted veggies or moldy and rotten.

Up to nearly 10% of Americans may be infected with brain parasites found in undercooked meat. One example is the brain-invasive pork tapeworm, which is the most common cause of adult-onset epilepsy. Allergenic fish worms found in almost 66% of retail fish tested can trigger allergic reaction in delicate/sensitive people.

There have been migratory skin worms found in half-cooked fish (like in sushi). Cheese may contain parasites and slimy parasites and organ meats may contain different worms. Cheese: asiago, bel paese, bleu/blue, brick, brie, camembert, emmental, gorgonzola, gruyere, muenster, port de salut, roquefort, stilton, swiss, pork Nearly 95% of tested retail U.S. meat (including burgers) has been observed to be parasite plagued. 

The meat business has reacted to this issue by encouraging arsenic to chickens and turkeys to reduce the parasite load; this arsenic might be connected to increased of cancer risk in customers, and adding bacteria-eating viruses to meat would not help one to keep away the brain parasite, toxoplasma, the second leading reason for foodborne sickness related death  in the US. 

Being bitten by the outer parasite, a lone star tick, may result in developing an allergy to meat. Anti-parasite diet Avoid cheese, under-cooked meat, salads and produce not properly washed with vinegar or salt water, over ripe fruits, eat limes and berries, pineapple and papaya, sweet potatoes or yams, pine nuts, and eat less on fermented foods (except fiber-rich). Consume less fat and sugar filled and processed foods but eat more fiber-rich foods, freshly cooked and well cooked.

Combine meat with veggies. Eat less fermented veggies and alcohol drinks. Add cabbage, tomatoes and lemon when cooking fish or meat to kill the parasites. Boil milk if you wanted to drink 2% milk. Add garlic, onions and sulfur rich foods in your meals daily. Eat well washed raw carrots and garlic. Have a banana at night (not over ripe). Avoid caffeine and chocolate until you have completed your anti-parasitic meds.

Lowering your fat intake from keto diet, lowers the supply of cholesterol for parasites to thrive. Use all kinds of coconut from oil to milk. Do not consume 3-day old rice or left over foods. Wear gloves when washing fish. Promote good hygiene. Freeze fish for portion you cannot eat within 2 days. Do not eat wilted veggies or moldy and rotten.

More tips

  • Avoid simple carbohydrates, such as those found in refined foods, fruits, juices, dairy products, and all sugars, except honey.
  • Eat more raw garlic, pumpkin seeds, pomegranates, beets, and carrots, all of which have been used traditionally used to kill parasites. In one study, researchers found that a mixture of honey and papaya seeds cleared stools of parasites in 23 out of 30 subjects. Drink a lot of water to help flush out your system.
  • Eat more fiber, which may help get rid of worms.
  • Probiotics (Lactobacillus acidophilus, Lactobacilus plantarum, Saccharomyces boulardii, and bifidobacteria). Help keep your digestive tract healthy. Probiotics may not be appropriate in some severely immune compromised patients. Talk to your doctor.
  • Digestive enzymes will help restore your intestinal tract to its normal state, which makes it inhospitable to parasites. Papain is an enzyme from the papaya plant that may help kill worms when taken 30 minutes before or after meals. Papain may increase bleeding in people with clotting disorders, or in those taking blood-thinning medications, such as warfarin (Coumadin) among others.
  • Vitamin C. Supports the immune system. Lower the dose if diarrhea develops.
  • Vitamin A (VitA) is a micronutrient that is crucial for maintaining vision, promoting growth and development, and protecting epithelium and mucus integrity in the body. VitA is known as an anti-inflammation vitamin because of its critical role in enhancing immune function.
  • Zinc. Supports the immune system. Zinc may interact with certain medications, particularly some antibiotics, and it may not be appropriate for people with HIV/AIDS. Talk to your doctor.
  • Niacin deficiency in pellagra associated with certain parasites, seems to be due to the impairment in the further degradation of 3-hydroxykynurenine to niacin.

Herbs

Herbs are a way to strengthen and tone the body’s systems. As with any therapy, you should work with your doctor to diagnose your problem before starting treatment. You may use herbs as dried extracts (capsules, powders, or teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). People with a history of alcoholism should not take tinctures.

Many of the herbs used to treat intestinal parasites have toxic side effects or interfere with other medications. Use them only under the supervision of a qualified practitioner. Your health care provider should treat you with the most gentle herb that is effective for the type of parasite you have. A few of the herbs that your provider might consider include:

  • Garlic (Allium sativum)
  • Barberry (Berberis vulgaris)
  • Goldenseal (Hydrastis canadensis)
  • Oregon grape (Berberis aquifolium)
  • Anise (Pimpinella anisum)
  • Wormwood ((Artemisia annua))
  • Curled mint (Mentha crispa)
  • Black walnuts (Juglans nigra)

For more related topics, see ebook of Connie Dello Buono at Balboa Press

https://www.balboapress.com/en/bookstore/bookdetails/807766-curated-health-tips-and-cancer-free-healing-ways

High LDL cholesterol linked to early-onset Alzheimer’s

This shows the outline of a head

HIGH LDL CHOLESTEROL LINKED TO EARLY-ONSET ALZHEIMER’S

Elevated levels of LDL cholesterol has been linked to an increased risk of early-onset Alzheimer’s disease, in those with and without a genetic risk factor. This suggests cholesterol could be an independent risk factor for dementia. Additionally, researchers identified a potential new genetic risk factor for early-onset Alzheimer’s, a rare variant of the APOB gene. READ MORE…
Image shows an alzheimer's brain slice.

FINDINGS SUPPORT ROLE OF VASCULAR DISEASE IN DEVELOPMENT OF ALZHEIMER’S

A new study reports midlife vascular risk factors are associated with elevated levels of amyloid beta in later life. READ MORE…

Depriving Deadly Brain Tumors Of Cholesterol , parasites need cholesterol

Depriving Deadly Brain Tumors Of Cholesterol May Be Their Achilles’ Heel

Summary: Depriving glioblastoma brain cancer cells of cholesterol caused tumor regression and prolonged survival in mouse models of the disease, a new study reports.

Source: UCSD.

In mouse models, alternative approach proves promising against hard-to-treat cancer.

Researchers at University of California San Diego School of Medicine, Ludwig Institute for Cancer Research and The Scripps Research Institute, with colleagues in Los Angeles and Japan, report that depriving deadly brain cancer cells of cholesterol, which they import from neighboring healthy cells, specifically kills tumor cells and caused tumor regression and prolonged survival in mouse models.

The findings, published in the online October 13 issue of Cancer Cell, also present a potential alternative method for treating glioblastomas (GBM), the most common and most aggressive form of brain cancer. GBMs are extremely difficult to treat. The median survival rate is just over 14 months, with few treated patients living five years or more past diagnosis.

Adult brain cancers are almost universally fatal, in part because of the biochemical composition of the central nervous system (CNS) and the blood-brain barrier, which selectively and protectively limits the passage of molecules from the body into the brain, but which also blocks most existing chemotherapies, contributing to treatment failure.

This includes blocking small molecule inhibitors that target growth factor receptors, which have not proven to be effective with brain cancers, possibly due to their inability to get past the blood-brain barrier and achieve sufficiently high levels in the central nervous system.

“Researchers have been thinking about ways to deal with this problem,” said senior author Paul S. Mischel, MD, a member of the Ludwig Cancer Research branch at UC San Diego and professor in the UC San Diego School of Medicine Department of Pathology. “We have been challenged by the fact that GBMs are among the most genomically-well characterized forms of cancer, with clear evidence of targetable driver oncogene mutations but this information has yet to benefit patients, at least in part, because the drugs designed to target these oncogenes have difficulty accessing their targets in the brain. We have been trying to find an alternative way to use this information to develop more effective treatments.

“One such approach stems from the observation that oncogenes (mutated genes) can rewire the biochemical pathways of cells in ways that make them dependent on proteins that are not themselves encoded by oncogenes. Targeting these ‘oncogene-induced co-dependencies’ opens up a much broader pharmacopeia, including the use of drugs that aren’t traditionally part of cancer drug pipelines but have better pharmacological properties.”

In previous research, Mischel and others had noted GBM cells cannot synthesize cholesterol, which is vital to cell structure and function, particularly in the brain. Instead, GBM cells derive what they need from brain cells called astrocytes, which produce cholesterol in abundance. Roughly 20 percent of total body cholesterol is found in the brain.

When normal cells have sufficient cholesterol, they convert some of it into molecules called oxysterols, which activate a receptor in the cell’s nucleus — the liver X receptor (LXR) — to shut down the uptake of cholesterol.

“So when normal cells get enough cholesterol, they stop making it, stop taking it up and start pumping it out,” said Mischel. “We found that in GBM cells, this mechanism is completely disrupted. They’re like parasites of the brain’s normal cholesterol system. They steal cholesterol and don’t have an off switch. They just keep gobbling the stuff up.”

Image shows an MRI brain scan of a glioblastoma patient.

GBM cells ensure their cholesterol supply by suppressing the production of oxysterols, the researchers said, ensuring cells’ LXRs remain inactive.

The research team, including Andrew Shaiu and Tim Gahman of Ludwig’s Small Molecule Development team at UC San Diego, identified an experimental metabolic disease drug candidate named LXR-623 that activates LXRs.

In mouse models, LXR-623 easily crossed the blood-brain barrier to bind with LXRs in normal cells, stimulating the production of oxysterols and the reduction of cholesterol. There was no effect upon healthy neurons and other brain cells, the scientists found, but GBM cells were deprived of vital cholesterol, resulting in cell death and tumor regression.

“Disrupting cholesterol import by GBM cells caused dramatic cancer cell death and shrank tumors significantly, prolonging the survival of the mice,” said Mischel. “The strategy worked with every single GBM tumor we looked at and even on other types of tumors that had metastasized to the brain. LXR-623 also had minimal effect on astrocytes or other tissues of the body.”

Mischel suggested the GBM strategy could be implemented in clinical trials using drug-candidates under development or in early trials.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Co-authors of this paper include: first author Genaro R. Villa, Yuchao Gu, Xin Rong, Cynthia Hong, Timothy F. Cloughesy, UCLA; Jonathan J. Hulce, Kenneth M. Lum, Michael Martini and Benjamin F. Cravatt, TSRI; Ciro Zanca, Junfeng Bi, Shiro Ikegami, Gabrielle L. Cahill, Huijun Yang, Kristen M. Turn, Feng Liu, Gary C. Hon, David Jenkins, Aaron M. Armando, Oswald Quehenberger, Frank B. Furnari, and Webster K. Cavenee, UC San Diego; and Kenta Masui and Peter Tontonoz, Tokyo Women’s Medical University.

Funding: Funding for this research came, in part, from the National Cancer Institute (F31CA186668), the National Institute for Neurological Diseases and Stroke (NS73831, NS080939), the Defeat GBM Program of the National Brain Tumor Society, the Ben and Catherine Ivy Foundation, the Ziering Family Foundation and the National Institutes of Health (CA132630).

Source: Scott LaFee – UCSD
Image Source: NeuroscienceNews.com image is credited A. Christaras.
Original Research: The study will appear in Cancer Cell.


All parasites may be metabolising cholesterol

The requirement of cholesterol for internalization of eukaryotic pathogens like protozoa (Leishmaniasis, Malaria and Toxoplasmosis) and the exchange of cholesterol along with other metabolites during reproduction in Schistosomes (helminths) under variable circumstances are poorly understood. In patients infected with some other helminthes, alterations in the lipid profile have been observed. Also, the mechanisms involved in lipid changes especially in membrane proteins related to parasite infections remain uncertain. Present review of literature shows that parasites induce significant changes in lipid parameters, as has been shown in the in vitro study where substitution of serum by lipid/cholesterol in medium and in experimental models (in vivo). Thus changes in lipid profile occur in patients having active infections with most of the parasites. Membrane proteins are probably involved in such reactions. All parasites may be metabolising cholesterol, but the exact relationship with pathogenic mechanism is not clear. So far, studies suggest that there may be some factors or enzymes, which allow the parasite to breakup and consume lipid/cholesterol.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142336/

Unsterilized milk

Raw (Unpasteurized) Milk | Features | CDC


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Raw Milk – North Dakota Department of Health