NEWS UPDATE-A NEW MILESTONE IN THE DIAGNOSIS OF PD

MILESTONES IN THE DIAGNOSIS OF PARKINSON DISEASE

A new hope has emerged for the early accurate diagnosis for Parkinson's Disease after research finding that an abnormal protein associated with PD can be detected from the patient's spinal fluid in clumps.

Though it is too early to say about a conclusive result for the test as it has been done with a small batch of the patients only but the researches say in future the test would be conducted through large batches of patients to bring up to surface.

As we all from a previous post in this blog about Parkinson's Disease PD, that PD is an incurable disease. It is a kind of nerve disorder in which dopamine production in the brain is impaired over time due to the damage and death of dopamine-producing neurons in the nigrostriatal pathway and substantia nigra.For details please refer to the article-Parkinson's Disease in this blog.

At present there is no proper diagnosis for PD to give a definitive result. Nowadays the diagnosis by a simple assessment through the patient's medical history, medical examination, physical and neurological tests. But the results are not immediate and may take years to conclude.

Dr.Allison Green and his colleagues of the National CJD Research and Surveillance Unit at the University of Edinburgh in the UK revealed that the diagnostic which they devised for detecting Creutzfeldt-Jacob Disease(CJD) rare serious dementia with complicated brain disorders, can be successfully used to diagnose and detect early development of PD. In CJD and PD the same clumpings of proteins are seen in the CNS fluids.

Dr.Allison Green called the test as Real-Time Quaking Induced Conversion(RT-QuIC). The test accurately detected the accumulation and clumping of Alpha Synuclein in the spinal fluid of PD patients.

Alpha-Synuclein 

This is a kind of protein found in all normal individuals but is believed to trigger PD and Lewy body Dementia by the formation of clumps in the spinal fluid. The clumps are known as Lewy Bodies.

These clumps are detected in the spinal fluid to determine and indicate the presence of these clumps present in the neurons of the nigrostriatal and substantia nigra and block them not to produce dopamine.

Also they block the dopamine production at the neurons situated in the region of cognitive abilities and cause the disease Lewy body Dementia and CJD.

At present the test by Dr. Green et.al has been applied to 20 samples of spinal fluid taken from PD patients and 15 samples from healthy patients.

The test however has the ability to measure the stickiness and clumping up of proteins an indicator of whether they are likely to cause the disease or not.

They found that the test was with 95% accuracy and 100% specificity.

THE NEWS

 

Early Parkinson's diagnosis moves closer with new protein test

Written by Honor Whiteman

Published: Tuesday 30 August 2016 Published: Tue 30 Aug 2016

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Researchers may be one step closer to a diagnostic test for Parkinson's disease, after finding that an abnormal protein associated with the illness can be detected in patients' spinal fluid.

Researchers are closer to a much-needed diagnostic test for Parkinson's disease.

While it is early days for the test, the team's results - published in the journal Annals of Clinical and Translational Neurology - have been hailed "hugely promising."
Parkinson's disease is a neurological condition whereby the production of dopamine in the brain is reduced over time, due to the damage and death of neurons that produce it. Dopamine is a neurotransmitter involved in the regulation of movement and coordination.
As a result, patients with the disease may experience tremors of the hands, arms, legs, jaws, and face, slowed movement, muscle rigidity, impaired posture and balance, and speech problems.
There is currently no definitive test for Parkinson's. The disease is normally diagnosed thorough assessment of the patient's medical history, a medical examination, and physical and neurological tests, but this can take years.
Now, Dr. Alison Green, of the National CJD Research & Surveillance Unit at the University of Edinburgh in the United Kingdom, and colleagues reveal how a test originally developed to detect Creutzfeldt-Jakob disease (CJD) could be adapted to detect Parkinson's.

The test detected Parkinson's with 95 percent accuracy

In their study, Dr. Green and the team report how the test - called the real-time quaking-induced conversion (RT-QuIC) - accurately detected accumulation of the protein alpha-synuclein in the spinal fluid of patients with the disease.

Fast facts about Parkinson's

• Almost 1 million Americans are living with Parkinson's
• The precise cause of Parkinson's remains unclear
• There is no cure for Parkinson's, only treatments to help manage symptoms.

Learn more about Parkinson's

Alpha-synuclein is a protein believed to be associated with the onset of both Parkinson's disease and Lewy body dementia.
In people with Parkinson's, the protein has been found to form clumps - called Lewy bodies - in neurons that produce dopamine, while in patients with Lewy body dementia, the clumps form in neurons associated with cognitive abilities.
While previous studies have attempted to develop a test to detect alpha-synuclein, these have produced conflicting results. This is because the protein is present in the brains of healthy individuals, only causing problems when it clumps together.
The test from Dr. Green and colleagues, however, has the ability to measure the stickiness and buildup of proteins, an indicator of whether they are likely to cause disease.
For their study, the researchers applied the test to 20 samples of spinal fluid taken from patients with Parkinson's disease, alongside samples of 15 healthy controls.
They found the test was able to identify 19 out of 20 samples with 95 percent accuracy and 100 percent specificity. It was also able to detect the buildup of the protein in three spinal fluid samples of individuals at high risk for Parkinson's.
The team also applied the test to samples of patients with Lewy body dementia. Compared with control samples, the test was able to detect the disease with 92 percent accuracy and 100 percent specificity.

A 'significant development' toward early test for Parkinson's

While these results need to be validated in a larger sample of patients, the researchers are hopeful that their findings could lead to much-needed diagnostic tests for both Parkinson's and Lewy body dementia.
Dr. Green says earlier diagnosis for these patients may mean greater participation in clinical trials of new drugs to prevent disease or slow progression.
Dr. Beckie Port, senior research communications officer at Parkinson's UK, says the team's findings could one day meet the need for a simple, accurate test for Parkinson's.

"Although early days, the fact that researchers have developed a new test that is able to detect abnormal alpha-synuclein in the spinal fluid of people with Parkinson's with remarkable specificity and sensitivity, is hugely promising.
Further research is needed to test more samples to see if the results continue to hold true, but this could be a significant development towards a future early diagnostic test for Parkinson's."

Dr. Beckie Port

Read about the discovery of a mutant gene interaction that could lead to new treatments for Parkinson's.

Written by Honor Whiteman

NEWS UPDATE-CALORIE BURNING GOOD FAT

CALORIE BURNING GOOD FAT

 

Recent research by UC San Francisco Researchers has revealed that there are two kinds of fats in our body is functioning for utilizing and storing the fat.

The researchers have studied brown fat which they called Beige Fat which they say burn the fat into calories and can help to ward off obesity and diabetes.

Also they said the beige fat if left with the unavailability of sufficient fat to burn they will convert themself into energy-storing white fat which causes obesity and diabetes. Hence the beige fat is having an ability to switch back and forth between energy hoarding white state and energy-burning brown state.

The beige fat is containing in its mitochondria which are deposited as brown pigments and give the brown color.

Infants and babies in their growing state are well provided with brown fat which helps the baby to comfort with heat during cold weather by burning the fat into heat.

All mammals including humans have two types of fat with entirely opposite functions. White fat which stores energy and is causing obesity and diabetes, brown which burns fat into calories and utilizes it causes leanness.

A lean person may have more brown fat and a fat person may have more white fat.

Unlike in babies the adult brown cells if left unattended with eating fat-free food then digest their own mitochondrial cell pigments which gave them brown color and become white fat. But this converted beige fat has the ability to switch back again into brown pigmented fat by a not well-described mechanism. In adults the beige brown fat cells are embedded into the white fat cells.

Genes play an important role in digesting their own mitochondrial pigments by the brown fat and become white.

The brown beige fats are active according to the temperature change or stress. Just a two-ounce of the brown fat can burn up to 200 calories a day when the temperature drops. But this does not work out in obese people as they do not have sufficient brown fat.

Also these approaches have dangerous cardiovascular side effects.

When the researchers removed the causative genes in mice to prevent the brown fat cells from eating their own mitochondrial pigments they succeeded in sustaining the brown cells and its benefits.

THE NEWS

Calorie-burning 'good' fat can be protected, says study

Adapted Media Release

Published: Monday 29 August 2016 Published: Mon 29 Aug 2016

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UC San Francisco researchers studying beige fat - a calorie-burning tissue that can help to ward off obesity and diabetes - have discovered a new strategy to cultivate this beneficial blubber.
Beige fat cells have the ability to switch back and forth between an energy-hoarding "white" state and an energy-burning "brown" state, the new research found, based on how they handle the cellular power plants known as mitochondria: Preventing beige fat cells from digesting their own mitochondria traps them in the energy-burning state. In mice, this intervention successfully protected against obesity and pre-diabetic symptoms, raising hopes for future applications in human patients.
The results - which appear in the journal Cell Metabolism - represent a key new advance in efforts to use beige fat to battle the growing worldwide epidemics of obesity and type 2 diabetes, according to senior investigator Shingo Kajimura, Ph.D., an associate professor of cell and tissue biology in UCSF's School of Dentistry.

Research may aid efforts to enhance and maintain energy-burning fat in humans

All mammals, including humans, have two types of fat with completely opposite functions: white, which stores energy and is linked with diabetes and obesity; and brown, which produces heat by burning energy and is associated with leanness.
Human babies are born with brown fat as a natural defense against cold, but it wasn't until 2009 that researchers first discovered that adult humans have energy-burning fat as well. In 2015, Kajimura's group demonstrated that most of this healthy fat in humans is not so-called classical brown fat of the type that babies are born with, but a completely different type of cell, which the researchers dubbed "beige fat." Beige fat is found within white fat and has the ability to quickly convert from an energy-storing state to an energy-burning state in response to environmental changes, such as cold or other stressors.
Many obesity researchers hope to harness the energy-burning capacity of beige and brown fat to help patients lose weight: just two ounces of the stuff can burn up to 200 calories a day when the temperature drops. But just exposing patients to cold temperatures - or giving them drugs that trick the body into thinking it's cold - have proven ineffective in early trials because most people who are obese lack a significant amount of active brown fat. These approaches also have dangerous cardiovascular side effects, which are of particular concern in obese patients.
Kajimura's group recently identified new pharmacological strategies for transforming white fat into beige fat in mice, which showed significant health benefits without cardiovascular side effects. However, the researchers soon realized that when these drug treatments are stopped, the new beige fat just reverts to white fat again within weeks.
"For many years our focus has been on learning to convert white fat into beige fat," said Kajimura, who holds joint appointments at UCSF's Diabetes Center and at the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research. "Now we're realizing we also have to think about how to keep it there for a longer time."

NEWS UPDATE-SOLUBLE CORN FIBER (CSF) HELPS BONE RESORPTION

SOLUBLE CORN FIBER AND CALCIUM RESORPTION

The article is based on the new research from Purdue University, West Lafayette, Indiana reveals that Soluble Corn Fiber (CSF) supplementation significantly helps the bone to better absorb and utilize calcium in women at their teens and post menopause periods.
CSF is a non-digestible carbohydrate present in packed foods, such as cereals, bread, and bakery items. Also used in beverages, frozen foods, candies, carbonated and flavored water.
SCF is added to packed edibles to compensate for their loss of dietary fibers while processing.SCF is having all benefits of intact dietary fibers found in grains, legumes, veggies, and fruits plus the recent research has revealed that it improves intestinal regularities and has prebiotic properties.
Moreover SCF improves healthy blood glucose and improves bone health by increasing calcium absorption.
The research reveals that SCF a prebiotic supports the body better absorb and utilize calcium during both adolescence and post-menopause. The gut microbe flora plays an important role in this by breaking the SCF to be used by the body very easily.
Commercially the SCF is available in the brand of Promotor Dietary Fiber and labeled as Maltodextrin. The product is manufactured by Tate & Lyle Ingredients America LLC who funded the research.
The research detailed their findings that after CSF passes through the gut unlike the intact dietary fibers these soluble fibers are digested and broken down by the gut flora to short-chain fatty acids which helps in the maintenance of bone health

THE STUDY

 n the postmenopausal study, 14 healthy postmenopausal women in three groups. The first group consumed 0 grams, the second group 10 grams, and the third group 20 grams of SCF every day for 50 days. The women in the groups that received 10 grams and 20 grams - amounts that are found in supplement form - displayed bone calcium retention improvement by 4.8 percent and 7 percent, respectively.

"If projected out for a year, this would equal and counter the average rate of bone loss in a post-menopausal woman," says Weaver, an expert in mineral bioavailability, calcium metabolism, botanicals, and bone health.

In the adolescent study, 28 girls aged between 11-14 years old consumed either 0 grams, 10 grams, or 20 grams of SCF every day for 4 weeks, while maintaining their regular diet. The females in both the 10 gram and 20 gram SCF groups saw an increase in calcium absorption by around 12 percent, which would build 1.8 percent more skeleton per year.

Gastrointestinal symptoms were minimal in both studies and the same was seen in the control groups.

"Most studies looking at benefits from soluble corn fiber are trying to solve digestion problems, and we are the first to determine that this relationship of feeding certain kind of fiber can alter the gut microbiome in ways that can enhance health," Weaver said. "We found this prebiotic can help healthy people use minerals better to support bone health."

LOW CARB DIET-FREE E-BOOK

LOW CARB DIET-FREE E-BOOK

Diet plays an important role in our body health.

Carbohydrates are the best sources of energy. Carbohydrates in our food are hydrolyzed into more water-soluble and absorbable monosaccharides such as glucose and fructose. Glucose is the more common form of carbohydrate source of energy for our body. Fructose may give some energy sources but not as much as glucose.

Fructose and glucose both increase total body fats and hypertriglyceridemia and abdominal fat.

In that sense beware that fructose increases.

triglycerides level double the amount of what glucose does. 

Fructose does not need to be digested and does not need insulin to be metabolized. Most of the fructose goes into the liver. Accumulation of fructose in the liver imposes heavy load to it and may cause liver damages.

The liver processes fructose into glycerol which will increase triglyceride levels

Glucose decreased HDL level while fructose increases it.

Glucose increases insulin sensitivity but fructose decreases it.

Diet contains only fructose may cause diabetes mellitus because of the total loss of insulin sensitivity.

Fructose has a low glycemic index but this is not the only factor to decide whether a diet is healthy.

Both sugars cause diabetes and obesity.

Glucose causes more weight gain than fructose.

A low carb diet should be practiced to reduce obesity, sugar, and to lead a healthy life. To download a fresh copy of an E-Book regarding Low Carb Diet which is absolutely free for our site visitors please click here

PART-5-RHEUMATOID ARTHRITIS

SECOND LINE DRUGS-Contd.

Corticosteroids

Corticosteroids are mostly glucocorticoids used as anti-inflammatory drugs. They are cortisol analogs.

In severe progressive RA prednisone can give some benefits. Because of the seriousness of side effects corticosteroids are considered to be the drugs of last choices.

They are used in,

1.Acute flare-ups of the disease

2.As adjuncts with other slow-acting drugs

3.In elderly patients as alternatives for more toxic second-line drugs

4.In patients who cannot tolerate or who are allergic to NSAIDs.

5.In patients with a systemic attack of RA.

Administration and Dosage

Oral prednisone is 5 to 10mg may be enough to some patients

Because of the serious adverse effects dosage should be limited to possible low with care.

If pain is localized to one or few inflamed joints an intraarticular injection may be beneficial.

Side Effects

1. Immunosuppression leads to delay in wound healing

2.G.I.Bleeding

3.Myopathy

4.Cataracts

5.Hyperglycemia

6.Hypertension

7.Osteoporosis

Topical Treatments

Topical treatments are safer but less systemic. They are counter irritants and rubefacients.

Capsaicin which is a pungent hot ingredient of pepper can be used as a rubefacient to relieve RA.

Capsaicin is blocking the substance-P which transmits the pain impulses from the periphery to the brain through sensory nerves.

Capsaicin can be applied three or four times a day to get good relief.

It is available in the market by the brand Zostrix

Counter Irritants 

1.Allyl isothiocyanate

2.Methylsalicylate

3.Menthol

All the above drugs produce mild counter inflammations and thereby relieve the RA pain.

They should be applied to the skin followed by gentle massages.

PART-4-RHEUMATIC ARTHRITIS

SECOND LINE DRUGS-Contd...

5.Penicillamine:-

The mechanism of its anti-rheumatic action is due to its ability to alter the immune response of the body. Penicillamine used to treat refractory rheumatoid arthritis. Its use is now very limited with more modern medication with fewer side effects.

Chemically penicillamine is a breakdown product of penicillin.

It delays the onset of joint erosions in RA.

Absorption

Penicillamine should be given in an empty stomach as food may interfere with its potency and block its absorption. As penicillamine is a chelating agent it may chelate all polyvalent ions present in the food such as calcium, magnesium, copper, iron, and zinc. These chelates are not absorbed by the intestine.

Dosage

The initial dosage is 125 - 250 mg once daily. Then the dosage is doubled after 3 months. After the next 3 months again the dose is doubled to a maximum of 750 mg daily until to get a required therapeutic effect. Very rarely the daily dosage can be maximized to 1000 to 1500mg under strict supervision. The basic dosing moto for this drug is to go low-go slow.

Side Effects

1.Reversible side effects such as rash, fever, blood urine, proteinuria, dysgeusia(distortion of the taste sense) and aphthous ulcers(mouth ulcers)

2.Vascular complications like leukopenia, thrombocytopenia and aplastic anemia

3. Systemic Lupus Erythematosus, Good Pasteur's Syndrome, and pemphigus have occurred. All these are autoimmune diseases in which the body's own immune system wrongly attacks its own skin, kidneys, and lungs.

6.Azathioprine

 

It is an autoimmune suppressor. It is a purine analog. It is used as a last attempt if other agents are not responded (refractory RA)

The dosage is 50 to 100 mg twice daily (1mg/kg). After 6 to 8 weeks the dose can be increased by ever 4 weeks by 0.5mg/kg.to a maximum of 2.5mg/kg.daily.

The dosage should be reduced in patients with renal dysfunctions.

Side Effects

1.Gastrointestinal effects such as nausea, vomiting, stomach pain,

2.Liver damage

3.Bone marrow suppression

4.Lymphoma

7.Cyclophosphamide

 

Similar to other immunosuppressive agents this antineoplastic agent can also be used in the treatment of refractory RA. But the use is limited because of its severe toxicity when compared with other immunosuppressive agents.

The initial dose is 1.5 to 3 mg/kg of the body weight.

Side Effects

1.Bone marrow depression

2.hemorrhagic cystitis

3.steriliy

4.Alopecia

5.Bladder cancer.

Other similar drugs are chlorambucil, cyclosporine. These are also immunosuppressive agents used in neoplastic treatments with a high toxic profile. Used to treat refractory RA.

Minocycline an antibiotic that can affect the Mycoplasma organism, the organism which causes RA.

PART-3-RHEUMATOID ARTHRITIS

RHEUMATOID ARTHRITIS-Contd...

Second Line Drugs

Unlike drugs like aspirin and NSAIDs which are considered as fast-acting and first-line drugs these drugs are said to be slow-acting anti-rheumatic drugs(SAARD) or disease-modifying anti-rheumatic drugs (DMARDs).

When a patient suffers from sustained disabilities with RA only an anti-inflammatory course is not sufficient. The course of the disease should be modified to ease the disability. This is possible with second-line drugs like hydroxychloroquine, methotrexate, gold compounds, penicillamine, and sulfasalazine. These drugs are used as an adjuvant along with the anti-inflammatory treatments. 

These drugs are acting by delaying or modifying the development of the disease. Therapeutic effects may take several months. Careful monitoring of the patients must be necessary because of the serious side effects.

In general these drugs are used along with anti-inflammatory drugs. But some doctors may initiate with these drugs alone and interchange them if they found one drug is ineffective. The ineffective drug should be discontinued before changing to other drugs.Initiating a second-line drug is possible if the patient is not tolerating anti-inflammatory drugs and their prolonged may result in some possible side effects. Yet these drugs too show potential side effects.

1.Hydroxychloroquine

 

The dosage is started with 200mg twice daily (400mg/day) or 6.5mg/kg whichever is less. It is possible as per the condition the daily dose can be reduced to 200mg once daily.

The patients should be taking care of the following side effects:-

1. Nausea and epigastric pain is possible but not seriously

2. Rare effects on eyes, skin, CNS, and bonemarrow are possible on the recommended dosage

3. Hydroxychloroquine causes retinal damage and hence visual checkup is recommended every 3 to 6 months by an eye specialist.

It is highly advisable to discontinue the medicine if the first sign of the retinal damage is notified.

4. Corneal damages can be reversible but the retinopathy is irreversible.

2.Methotrexate

As methotrexate acts faster than other second-line drugs some physicians are considering it as a first-line drug yet it is somehow slower than anti-inflammatory drugs.

Methotrexate is a folic acid antagonist and is used in many neoplastic disease treatments.

The initial weekly doses are 5 to 10 mg. This can be divided as twice-daily doses but is not safer and much beneficial.

The dosage can be slowly increased to 15 to 20 mg every 3 to 6 weeks. 

Intramuscular dosage also available if the oral route is ineffective or may produce gastric trouble.I.M.dosage is once per month.

The following precautions must be taken:-

Aspirin may increase the toxicity of methotrexate by delaying its excretion. Hence aspirin should not be used with it.

Adverse Effects

1. Gastric effects like nausea, anorexia, stomach cramps, and ulcers)

2.Bone marrow suppressions

3.Liver damage

4. Hypersensitivity reactions lead to pneumonitis

5. Rarely pneumonia and chickenpox may precipitate as the drug is immunosuppressive.

6.Monitor RBC, WBC, and platelet counts.

3.Gold Compounds

 

Gold compounds are proved as very effective second-line drugs in relieving RA by delay progressions of joint erosions.

a)Gold Sodiumthiomalate i.m.injection

b)Aurothioglucose i.m.injection

A test dose of 10mg is given followed by 25mg of the initial weekly dose for two weeks.

After that the dose can be increased to 50mg per week for 20 weeks can be given.

Once there is an expected effect occur the treatment should be continued with the same 50 mg dosage with 2 weeks intervals followed by every three weeks and then to reach every month for 3 to 6 months.

The treatments should continue as a monthly therapy. Abrupt discontinue of the treatment may result in a relapse of RA which may not respond again to gold therapy.

Side Effects

1.Proteinuria

2.Blood dyscrasias

3.Rashes

4.Leucopenia

5.Thrombocytopenia

6.Aplastic anemia

7.Anaphylaxis

8.Angioneurotic edema

9.Glossitis

10.Interstitial pneumonitis

11. Gold Sodium thiomalate because of its water solubility can produce vasodilation, hypotension, and syncope. These effects do not occur with aurothioglucose which is fat-soluble.

c)Auranofin(Oral)

This drug is orally active, less effective, and less toxic.

The initial dose is 3 mg twice a day or 6 mg once a day for six months.

If no effect the dose can be increased to 3 mg three times daily or 9 mg once daily.

Still there is no effect reached auranofin should be discontinued.

Side Effects

1.Diarrhea, stomach pain usually reversible

2. Rash and stomatitis also reversible

3. Proteinuria also reversible

4.Rarely bone marrow suppression and renal toxicity.

4.Sulphasalazine

 

Sulphasalazine is a sulphonamide derivative used as an anti-RA drug widely in many countries.

It is a very effective drug

It slows the progression of joint damage

It can be given orally.

The dose is 0.5mg twice daily.

The dose is slowly increased by 0.5mg every week up to 2 to 3 gram /day in divided doses.

Side Effects

1.G.I.Distress

2.Blood dyscrasias (Rare)

3.Hepatitis (Rare)