AUTOCOIDS AND ANTAGONISTS-PART-2

AUTOCOIDS-AUTOCOIDS ANTAGONISTS-Contd...

PROSTAGLANDINS

Chemically prostaglandins are derivatives of prostanoic acid a 20 carbon fatty acids contain a pentagonal carbon ring.

In general prostaglandins are synthesized by our body from fatty acid eicosatetraenoic acid or arachidonic acid. As being these are all eicosanoids they are considered as true hormones.

Prostaglandins are very important biologically active substances in our bodies identical to hormones. In the beginning they were extracted from the seminal secretions of prostate glands. But nowadays they are found to be present in almost all tissues of our body. Even a nanogram of the chemicals is biologically very active.

Classifications

Prostaglandins are classified as A, B, and E.

They are classically abbreviated as PGA, PGB, and PGE. These classifications are further differentiated and related to the presence or absence of keto or hydroxyl groups at positions 9 and 11.

Subscripts relate to the number and position of double bonds in the aliphatic chain.

Pharmacology

Endogenous prostaglandins are biological substances that affect many body functions.

Many external stimuli which may be chemical, mechanical insults are causing the release of prostaglandins which contributes to the signs and symptoms of the inflammatory processes such as reddening, edema, pain, and itching. 

Prostaglandin releases are responded by our body physiologically with vasodilation, in many vascular beds and vasoconstrictions in isolated areas.

Prostaglandin-Es inhibit platelet aggregation, relax bronchial and GI smooth muscle, contract uterine smooth muscle, and inhibit gastric acid secretion. The gastric acid secretion block is done along with Prostaglandin-I.

Alternatively the Prostaglandin-Ds and Fs are causing contractions of bronchial and gastric smooth muscle.

In general all prostaglandins are increasing renal blood flow, increase diuresis with loss of sodium, and potassium in urine but paradoxically increases renin secretion.

They also cause diverse endocrine and metabolic effects.

Clinical Indications

PG-E Analogues

Alprostadil (Prostin VR Pediatric):-It is used for temporary maintenance of a patent ductus arteriosus, in awaiting corrective surgery for congenital heart defects.

Alprostadil(Caverject) To treat impotence due to erectile dysfunction.

Misoprostol:-To prevent and treat NSAIDs induced gastric ulcers. To induce abortion.

Also the other PGE analogs such as Dinoprostone(Prostin-E2, Prepidil, Cervidil)and Carboprost(Hemabate) are used to induce safe abortion. Also they are used to ease the labor during pregnancy by inducing cervical ripening.

Side Effects

1.CNS effects:-

CNS irritability

Fever

Seizures

Headache

2.Cardiovascular effects:-

Hypotension

Dysrhythmias

Vasodilation

Flushing

Cardiac arrest

3.Respiratory depression

4.Hematologic:-

Anemia

Thrombocytopenia

Disseminated Intravascular Coagulation

5.Diarrhea

6.Renal dysfunction

7.Irregular spotty menses

8.Abortion

9.Pain at the penis

AUTOCOIDS AND AUTOCOID ANTAGONISTS-PART-1

AUTOCOIDS AND AUTOCOID ANTAGONISTS

Autocoids are endogenous chemicals by which the body heals and correct itself during some stressful and painful situations.

Auto means in Greek 'self' and Akos means 'medicine or remedy' and hence by the name they are body's 'self medicines'.

Autocoids are considered as true hormones that are secreted locally and are not secreted into the blood. But they involve a variety of pharmacological actions. Hence they are also considered as local hormones.

There are many prototype autocoids are secreted in our body. They are,

1.Histamine

2.Serotonin

3.Prostaglandins

4.Kinins

and others like leukotrienes, and interleukins etc.etc.But here we will deal with the first three autocoids as they are the prototypes and not secreted into the blood.

1.Histamine and Antihistamines

Chemistry

 Histamine is a bio-amine derived from the amino acid Histidine present in the protein-rich foods. Histidine an amino acid is decarboxylated by the enzyme L-histidine decarboxylase into histamine.

Histamine is widely present in the body in the granules of mast cells and basophils.

Mechanism and Effects

Histamine when released from the mast cells by external or internal allergen stimulants acts on its own receptors such as H-1 and H-2.

These receptors are located on our body cell surfaces and mediate numerous varieties of pharmacological responses.

Physiological Effects 

1.Constriction of bronchioles(H1)

2. Constriction of intestinal smooth muscle(H1)

3.Stimulates sensory nerves mediating pain and itching(H1)

4.Lower Blood Pressure (H2)

5.Stimulates gastric acid secretions(H2)

6.Increases permeability of skin capillaries(H2)

Clinically histamine has no medical use. But medicinally antihistamines have a variety of use.

Classifications

A.H-1 Antagonists

1.Ethylenediamine:-Tripelennamine

2.Alkylamines:-Chlorpheniramine maleate

3.Azines:-Promethazine

4.Piperidines:-Cyproheptadines

B.H-2 Antagonists

These are heterogenous congeners of histamine

1.Cimetidine

2.Ranitidine

3.Famotidine

4.Nizatidine

In general action of histamine on

1.H-1 Receptors

1.Allergy

2.Anaphylactic reactions such as bronchoconstriction, vasodilation, increased capillary permeability, and spasmodic contractions of Gastrointestinal smooth muscles.

2.H-2 Receptors

1.Increased gastric acid secretions

2.Increased pepsin secretion

3.Increased intrinsic factor (Castle's factor) formation

H-1 Antagonists

Competitively the inhibit the action of histamine on these receptors by their similarity of structures. Thus they limit the histamine effect on bronchial smooth muscle, capillaries, and GI smooth muscle.

These drugs also prevent the allergy-induced itching and pain of the skin and mucous membranes.

H-2 Antagonists

They limit the histamine effect of gastric acid secretions.

Therapy

Histamine has no medicinal and clinical value, yet it can be used as a diagnostic agent to test gastric function. However other gastric stimulants safer as diagnostic agents.

H-1 antagonists are mostly used as anti-allergic agents to reduce itching, urticaria, seasonal cold, and conjunctivitis.

H-2 antagonists are used to relieving from hyper acid secretions.

Toxicity

H-1 Antagonists:-

1.CNS depression

2.Sedation

3.Tiredness

4.Nausea and Vomiting

5.Anticholinergic effects such as dry mouth, urinary retention, and constipation.

Teratogenic effects(not suitable in pregnancy and lactation)

Peripheral H-1 antagonists such as terfenadine and astemizole are devoid of sedation fatigue and anticholinergic side effects.

But these drugs on elevation in plasma have serious cardiovascular effects such as QT prolongation in ECG, cardiac arrest, torsades de points, and ventricular arrhythmias.

Terfenadine is contraindicated with ketoconazole, macrolides as these compounds will reduce its liver metabolism and elevate plasma levels of terfenadine.

H-2 Antagonists:-

1.CNS effects like confusion and dizziness

2.Hepatic failure

3.Kidney failure

4. High doses of cimetidine cause androgenic effects like impotence and gynecomastia in men and galactorrhea in women 

NEWS UPDATE-MINIMALLY INVASIVE SURGERY-THE IKNIFE SURGERY

IKNIFE SURGERY

If anybody thought of going into the operation theater fills with trauma and fear of surgical instruments, the needles and knife's cutting edges. General anesthesia or partial anesthesia may minimize the pain but still they are problematic.

Whenever surgery is advised by the doctor the patient gets naturally the presurgical trauma and fear.

The history of surgery dates back to dark and more invasive methods. Ancient Egyptians drill holes into the living person's skull to cure a headache, migraine, convulsions, and to correct a fracture.

In ancient times a cataract surgery was carried out by passing a hook through the pupil without an anesthetic. Leeches were used to suck the blood which lets out during the surgery. Now these gruesome and invasive surgical operations become past history. Thank God as at present the surgery becomes mostly noninvasive by the inventions of most modern instruments such as Laparoscopy, and laser instruments. Even a heart transplant is now relatively routine. A gallbladder can easily be removed through a keyhole surgery by using a laparoscope.

A laparoscope is a small tube with a light source and camera which is inserted through a keyhole into the body until it reaches the relevant part. The areas that to be operated, show up on the screen.

Minimally invasive surgery involves, small incision, less scar, lower risk of infections, a reduced period of convalescence, and a shorter stay in hospitals.

ARTEMIS OR ROBOTIC OPERATIONS

In July 2000 a team of scientists in Germany developed an operating system with two robotic arms which are controlled by a surgeon at a control console. They called it Artemis.

In the same 2000, the first Robotic Surgical System was approved in the US by the FDA. They called it by the name The Da Vinci System.

The system contains three components.

1.A vision cart with a light source and cameras

2.A master console where the surgeon sits

3.A movable cart with two instrument arms and the camera arm.

The camera provides a true 3-D image displayed above the surgeon's hands so that the tips of the instruments seem like an extension of the control grips.

Foot pedals control extra cautionary, camera focus, instrument and camera arm clutches, and master control grips that drive the servant robotic arms at the patient side.

But still, there are drawbacks in the robotic surgery with reports of malfunctions, and errors which sometimes fatal. Hence these methods to not satisfied by everyone else.

ELECTROSURGICAL KNIVES

As days are passing the surgical science improves with higher technology to minimize the complications of surgery.

Electrosurgical knives are invented in 1920 and are used to remove cancerous tumors. The electrical knives are working by using an electric current it rapidly heats the body tissue and cutting it by minimal blood loss. Yet the instrument needs to be improved as the older electrical knives and the doctors' eyes cannot many times differentiate the cancerous cells from the noncancerous healthy cells.

In 2013 a continuous research on this has given the fruit by the finding of an Iknife with the expected result.

The Iknife by using mass spectrometry can enable the surgeon to examine biological tissue by pairing up electrosurgery.

In mass spectrometry electrically charged ions are passed through the electric or magnetic fields. These processes can distinguish between tissues of different combinations by the calculation of mass to charge measurements. The method is known as chemical profiling.

By analizing the chemical composition of different tissues, it can easily identify which tissues are healthy and which are not.

Mechanisms of the Iknife

Cutting with the electrical knife causes the tissue to vaporize and produce smoke. This smoke is sucked and passed through connected a mass spectrometer which analyzes the vapor to its chemical mass. By matching the results to a reference index, the surgeon can identify the type of tissue within 3 seconds.

The reference index has been made by Dr.Takas and his team by taking and comparing thousands of cancerous and non-cancerous tissues. From these samples they created the data index of 1624 cancerous and 1309 non-cancerous entries for matching samples in the future.

In future the Iknife can be used to analyze mucous membranes, and the respiratory, urinogenital, and gastrointestinal systems.

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