BODY FITNESS AND BLOOD CHOLESTEROL MANAGEMENT

Healthy Lifestyle And Cholesterol

Everybody in the world wants to enjoy a longer but healthy life.To lead a healthy life our over all body fitness our healthy mind,our food and family atmosphere all plays important roles.Hence Body Fitness is one important factor to have a healthy prolonged enjoyable life.In our body to keep it fit over all Cholesterol plays an imporant role.

Cholesterol Sructure

 

 Cholesterol is chemically a steroid as it is having the typical four ringed portion which is known as cyclo pentano perhydro phenantherenn  ring or steroidal ring  indicated by two arrows and carved by a circle in the picture above.Typically any compound which if it has this four membered ring in its chemical sructure is known as a steroid.But the word steroid was derived by a different methodology as follows.In greek stero means stone like solid.These compounds are mostly oily in nature oil soluble and easily solidyfy into stones in nature.The name cholesterol is derived from the Greek word Chole means bile and stero means solid and ol means an alcohol as first first cholesterol was identified from the extracted gall stones.But later on amazingly they find out that our entire body which is made out of numerous cell units which are all made out of cholesterol.
Humen and any animal cells in general cells of any vertebrates (The bony Living Things)  are differing from the plant and bacterial cells by devoid of a cell wall and instead of cell wall they contains cholesterol which covers the entire cell and protect the inner cell content.That is why humen and animal cells are more flexible and movable than the plant and bacterial cells which are more rigid.
 Cholesterol is available in our body in various forms as alcohol which is soluble in water and is esterified with our body fatty acids to form water insoluble fats.Cholesterol in our body available in high concentration in Liver,Spinal Cord and Brain.

Fats are storable substances which are oily in nature and are water insoluble are mostly stored in Adipose (Fatty) tissues for later consumption in emergency  in energy starving situation and in end stage ketonic Type-1 Juvanile Diabetes Mellitus.

Our body is getting fats mainly in two ways.First is the synthesis of Triglycerides,which are the esters formed by the esterification reaction between our body glycerol with three molecules of fatty acids.This synthesis is mostly performed in liver catalysed by insulin.Secondly the esterification of Cholestryl Alcohol or Cholesterol with a molecule of a fatty acid.This synthesis is performed in the entire body tissues especially Adipose Tissues,the tissues which is more vulnerable to become fatty

Interestingly most of our body steroids such as Adrenocorticosteroids and sex hormones are all prepared from Cholesterol as a base.Vitamin D3(Chole-calciferol) the important and more tolerable type than D2(Ergo-calciferol) in humen body is prepared from our body cholesterol when our body skin is exposed to the evening sun light

CHOLESTEROL IN THE BLOOD

As we have seen our body contains cholesterol in the form of soluble alcohol and fatty esters especially in the Adipose tissues,in he Liver,in the Brain in the Spinal chord and in the entire nervous systems.But on contrary in our cardio vascular system or simply in our blood cholosterol is circulating in a packed particles known as Lipoproteins.Esterified cholesterol and glycerol are naturally having a molecular structure similar to minute powdered small pieces of glass and they have sharp edges and hence they may damage the inner wall of the blood vessels if they circulate as they are without packed in as lipoproteins.See below the structure of a Low Density Lipoprotein (LDL) cholesterol 

 and note the arrows pointing the fat particles looking like broken glass pieces with sharp edges nicely packed inside with apolipoproteins,phopholipids and unesterified cholesterol.

Liver is one of the important organ which is synthesizing and releasing fatty esters in various form into the blood as LDL,HDL,VLDL,etc.The above figure is giving an outline diagrammatically.When we take fatty food especially dietary foods the fat in the food is first saponified by the alkaline inestinal juice and absorbed along with the food as large chylomicrons  and enter first into the lymphatic circulation and hen into the blood stream.These chylomicrons are large but very very  thin packets of fatty lipids mostly triglycerides covered by thin layers of lipoproteins,phospholipids and unesterified cholesterol. and carry them into tissues.Tissues hydrolyze the triglycerides into glycerol and fatty acids by the action of he enzyme Lipoproteinlipase.The free fatty acids are absorbed by the tissues and the remaining chylomicron remnents are taken by the liver.Thus liver gets milk fats.Thus chylomicrons carry exogenous fat in the blood for metabolism.

Cholesterol is produced in the liver as by the following map:-

In the liver the Acetyl Coenzyme-A is converted to mavalonic acid by HMG Co-A reductase and the mavalonic acid after underwent into various step is converted to cholesterol.Thus the increased cholestrol would supress the mavalonate pathways.Then again the cholesterol gets esterified to form various lipo proteins.Thus a reduction in cholesterol gears up the pathways on one side and the increase in LDL would induce more and more LDL receptors in the liver on he otherside and the cycle repeats.

DYSLIPIDAEMIA AND THE CORONORY HEART DESEASE 

                                          (CHD)

As we have seen previously our body contains cholesterol through out all the entire tissue cell units as the cell-wall,the entire nervous system including the brain and spinal chord  the liver, the adipose tissues, and the blood.Out of our total body cholesterol 90% produced by the liver endogenously and the remaining 10% only coming from food intake.Total cholesterol of our body should be at the range of 160mg to 200mg. see the chart.

                                                       

  Always remember that only total cholesterol may not be a correct indicator for you that you have CHD.Because some people have total cholesterol little out of range such as >260 but <400 may not have the risk of CHD.
On the otherhand CHD or Coronary Heart Desease is a fatal condition in which the coronory artery which supplies blood and energy to the heart may have some blocks due to athrosclerosis which is mainely due to the elevation of LDL cholesterol or bad cholesterol.Hence in your lipid profile you must watch the LDL and Triglyceride levels.Remember Triglycerides are not cholesterol but they are fatty esters formed by the esterification reactions between glycerol with three molecules of fatty acids
The normal levels of the Lipid Profiles are as follows:-
Total cholesterol                    > 190   and  < 210
LDL-C                                 > 90    and < 110
Triglycerides                         > 100   and < 150 
HDL-C                               > 40      and < 65 
If LDL-C elevated above the level then the symptoms are Pancreatitis tiredness fatigue and symptoms of CHD 
Here are formulas for finding out LDL-C cotents:-
LDL- Cholesterol     = Total Cholesterol-(HDL-C+VLDL-C)     VLDL=means very low density choles-                                                                                                   - terol whic is produced by live endogen-                                                                                                      -ously
LDL-Cholesterol     = Total Cholesterol - (HDL-C+ TG)              TG=means Triglycerides
If the Triglyceride levels are >400 then the above formula should be calculated with non  HDL-C as follows:-
LDL-Cholesterol    = Total Cholesterol - (HDL-C+ nonHDL-C)
non HDL-C           = Total cholesterol  - HDL-C

SYMPTOMS OF CHD OR  IHD (ISCHEMIC HEART DISEASE)

Ischemia is the condition in which blood flow to a particular area of the heart is blocked so that the area becomes dimmed or blackish  in colour because of there is lesser oxygen supply than the demand by the tissues of that area and the area is known as Ischemic

Reversible Angina is a condition in which there is a temporary insufficiency or blockade of blood and oxygen supply due to restlessness,stress,anxiety.The condition would releive after taking sufficient rest.

Acute Heart Attack(AMI) is a condition if Reversible Angina is allowed to persist for prolonged time without taking rest or medications like Nitroglycerin then the ischemia damages that part of the heart in which  it occured may presipitate Irreversible ischemia Or Acute Reversible Myocardial Infarction

Sudden Death is a condion in which if the acute reversible myocardial infarction is allowed to persists for prolonged time without proper hospitalization the result will be Irreversible Heart Attack or Sudden Death due to the fatal ventricular fibrillation   

  The first symptems of the CHD is chest pain or angina which will elevate from the chest and radiate to the left arm and further radiate to neck jaws and back  followed by sweating, unconciousness and heart attack which indicates that there is a complete blockade of the coronary blood circulation

A partial blockade will leads to a minor angina which will be similar to the symptoms of hyper acidity.
A mild or moderate angina is common in stressfull,and hard work,or sleeplessness condition but will be relieved by taking rest.But a severe angina as a result of complete blockade of arteries will eventually leads to Heart Attack or Myocardial Infarction which will damage the heart muscle permanently if not treated immediately may cause death.The severe anginal pain which means a heart attack will not be releived by taking rest or nitro glycerin.
There are other symptoms also common in heart attack such as 1.nausea 2.sweating 3.restlessness 4.loss of conciousness 5.breathlessness,
A severe chestpain lasting for more than 15 minutes indicates it is a heart attack.Usually a mild angina will relive if you take a rest or a nitroglycerin tablet.But heart attack would not get relieved by these.The heart attack can happen at any time even at rest.Some times without any painor symptom a heart attack may occur this is known as Silent Heart Attack .This is common in patients with Diabetes Mellitus 

Treatment Options For Dyslipidemia And CHD

The treatment according to the National Cholesterol Education Program Guidelines (NCEPG) should be based on the LDL-C level in the blood.Accordingly the base level line they fixed is = or > 190mg/dl.If a patient is having LDL-Cholesterol equals to or above the base level if he has no CHD or one or two strokes of CHD.

Usually hyperlipidemias are classified as per the causes of occurrence.

Primary Hyperlipidemias are caused by either genetic factors or environmental factors   e.g.Hyperchylomicronemia;Hypercholesteremia;Hyperlipidemia and Hyperglyceridemia

Secondary Hyperlipidemias are caused by other metabolic disorders such as Diabetes,Hypothyroidism ,

Renal Desease,and Alcoholism.  

Treatments  

1.First intervention is food control and exercises.Relaxed Walkings,and very light Aerobic Exercises
2.Bile acid binding resins such as Cholestyramine and Colestipol
   Bile acids are acting by forming insoluble complexes with bile acids which are the cholesterol raw materials and the insoluble complexes lateron would be excreted in stools.
3.HMG CoA Reductase Inhibitors (HMGCAR) such as various statins.To study further about STATINS clic here.
4.Fibric Acid Derivative such as Clofibrate,Gemfibrozil.For Mechanisms of actions and Side effects please click on the hyperlinks
5.Niacin

Fish Oils

Fish oils especially from Cod and Salmon fish livers are major sources for unsaturated fatty acids such linolenic acid and omega 3 fatty acids such as eicosapentanoicacid(EPA) and docosohexanoicacid(DHA).These linonenic acid also acids  on consuming is converted into eicsapentanoicacid(EPA) and docosahexanoic acid (DHA).
Fish oils because of their omega 3 poly unsaturated fatty acids contents are believed to reduce the synthesis of VLDL-C and LDL-C but enhance the metabolism of VLDL-C to LDL-C and thereby increase the LDL-C paradoxically The effect on HDL-C is uncertain.
Fish oil treatments are of little value unless the patient has to consume twice or thrice diets contains fish in a weak.
But the fish oils are reducing the risk of CHD because of their anti arrhithmic effect and less because of their lipid lowering effect.
The EHA and DHA competes with arachidonic acid for cyclo oxigenase enzyme to form the more potent platlet anti aggregator thromboxane A3 by which the blood becomes more thinner to fecilitate the circulation and thereby reduce the risk of CHD

Fat Management Programmes

For a complete pharmacology of Fat management to down load into your computer please click here

See the following video

 

ConclutionTotal cholesterol along with LDL-C and Triglycerides should be controlled within the limits as they are major causes for the Coronary Heart Disease (CHD).

Smoking,Alcohol,Obesity,And Diabetes Mellitus should be avoided.CHD may lead to fatal Myocardial Infarction if left untreated. 

Do regular excercises especially a morning and evening walks.

Thank you. 

TOP 10 FRUITS FOR LOWERING BAD CHOLESTEROL

 1.Avocados a large berry type fruit with a central stone like seed is rich in Mono Unsaturated and Poly Unsaturated Fatty Acids very similar to olive fruits.Scientists beleive that 75% of the unsaturated fatty acids are responsible for reducing LDL cholesterol

AVOCADO

2.Apples are really wonderful and miraculous fruits to lower LDL bad cholesterol.The researchers from the Florida State University in 2011 explained this in The Experimental Biology Meeting in Washington DC.

3.Strawberrys are beleived to have good anti oxidant properties and a recent researches by some Italian scientists also proved that strawberries are powerfully reducing bad LDL cholesterol and triglycerides as they enriched with mono unsaturated and poly unsaturated fatty acids.

  4.Oranges are though not having cholesterol but they have good fiber contents which is responsible for lowering cholesterol.Eventhough oranges are not placed in the top ten fruits to lower the cholesterol it is of having high beneficial effects to reduce cardio vascular insufficency,coronery heart disease because of its antioxidant properties.Oranges are rich in vit-C,flavenoids and enormous fibers.

5.Pineapples are found to be good for reducing bad cholesterol.Pineapple is rich in vitamins,minerals and fibers.Its main cotent Bromelin is said to be good for digesting,assimilating and metabolising proteins and fats.It also prevent excess fats hovering into the blood.

6.Grapes are tasty sweet juicy fruit available as black and green grapes.Grapes contains a chemica known as Pterostilbene this can reduce bad cholesterol and triglycerides in the blood just as a priscription medicine known as Ciprofibrate according to Dr.Agnes Rimendo,Ph.D of Department Agricultures National Products Utilization Research centre in Oxford,Mississippi.

7.Pomegranate not only reduce bad cholestrol it also protects HDL from damage.This is very important to those who are under metabolic woes such as overweight,obesity,devolopimg DM in which there are unprotected good cholesterol like HDL.Paraoxonase an enzyme which is helping HDL to absorb LDL before it gets broken and thus protecting the arteriolar wall.Pomegranate as well as Grapes are acting through this enzyme.

8.Lemon contains pectin an enzyme which is good for reducing bad cholestero along with Vitamin-C a powerful anti oxident and fibers which makes Lemon is a perfect fruit in the fight for bad cholesterol.

9.Grape fruit is one kind of a citrus fruit,Like other citrus fruits such as orange ,and lemon grape fruit also contains pectin,Vit-C,and fibers to lower the bad Cholesterol

 

10.Blueberry is the fruit very similar in appearance and taste to grapes and hence they too have the wonderful cholesterol reducing enzyme Pterostilbene which work very similar to the commercially available cholesterol lowering drug Ciprofibrate said by Dr.Agnes Rimendo,Ph.D of Department Agricultures National Products Utilization Research centre in Oxford,Mississippi.Also the blueberrys are rich in Vit-C and fiber contents which are also help to reduce bad cholesterol in the blood.
Click here to have a video entertainment regarding to this

GLUCOSE METABOLISM AND DIABETES MELLITUS

 Post-1:

Poop test can tell if you are diabetic, say docs

TNN | Mar 3, 2016, 07.09 AM IST

CHENNAI: Stool tests may gross out many people but doctors are increasingly taking a closer look at poop -to check if Indians are at greater risk of diabetes, obesity, and cardiovascular diseases.

Symptoms:

                  1. Sudden weight loss;

                  2. Frequent urination or Poly Urea and this symptom may be less common with Type-2 patients 
                  3.Too much thirsty or Poly-Dypsia
                  4.Too much hungry or Poly Phagia
                  6.Ketoacidosis, a condition at which ketone bodies are circulated all over the body tissues. This symptom is the immediate consequence in Type-1 D.M
                  7. Because sugar is excreted more in urine mostly the urinals or toilets is swarmed with 
                     ants and flies 
Diagnosis:1.At fasting, the test result will show the reading equals to or above 130 mg/dl
                   2. After the loading of a 75gm oral glucose dissolved in 300 ml water in a 12 hr fasting period if the test reading after a 2 hr test is equaled or above will confirm D.M

     INSULIN

CHEMISTRY: Insulin by itself is a polypeptide composed of two chains of aminoacids one below another as a double row linked by disulfide (sulfur-sulfur) bonds between cysteine residues as you can see in its molecular structure shown below. It contains a total number of 51 amino acids.

When Insulin binds to the cell receptors which is a tyrosine kinase present on the cell wall then the cell secretes transporters out to the cell membrane and these transporters in the presence of insulin carry glucose inside the tissue cell to metabolize it.
                                                           

There are various types and TREATMENTS are available to the disease

Type-1: Fully insulin-dependent as there is no secretion of insulin at all and daily intake of insulin is the primary treatment. A maximum of 10% of the people is affected by this type. Very rarely its by hereditary and by genetic transfer. It is mostly by body self-defending system otherwise known as autoimmunity as the pancreas of these patients are found with antibodies damaging beta islets.
Type-2: Partly Insulin-dependent or Fully Insulin Independent as insulin secreted not sufficiently in this type for the cells to respond.Various oral antidiabetic drugs with insulin if needed. Almost 90% of the people are suffering by this type. These types are mostly hereditary and genetic transfer.
Types of Insulin-A Brief
1)Short-Acting:-Insulin Lispro (Humalog) and regular (Humulin)
2)Medium Acting:-Isophane insulin suspension (NPH), and insulin zinc suspension
3)Long-Acting:-Insulin zinc suspension Extended(Ultra Lente)

Toxicology

1)Hypoglycemia (a sudden lowering of blood sugar)
2)Insulin Allergy
3)Insulin Antibodies
4Lypodystrophy-a change in the fatty tissue surrounding the injection site

Pharmacokinetics

Insulin: The Pharmacokinetics of insulin comprises of its absorption from the site of administration, distribution including attacked and neutralized by circulating antibodies, degradation, and excretion. The distribution and metabolism of insulin administered from outside that are exogenous follow exactly the same as how the endogenous insulin is done. But in certain circumstances, the exogenous insulin distributed may be resisted by produced and circulating antibodies which may cause insulin resistance may alter the kinetics, otherwise it cannot be actively changed. The use of preparation with low immunogenicity may reduce this variation.

The absorption process the details are still unknown is influenced by many variables some of which can be controlled, and thereby the differences can be reduced between individuals. Besides this, the volume and size of the doses, the timing between individual doses, the site of injection, and the type of insulin preparation and the permeability and blood flow of the injected tissue also influence the absorption.

Serum insulin may peak up to one hour after the injection, of soluble insulin into the thigh Vs into the abdominal wall.

Pharmacodynamics

Insulin after underwent to some kinetic process insulin reaches the site of its actions mainly the cell receptors. Once it got the reception well at the receptors (tyrosine kinase)on the cell membrane (remember insulin does not enter into the cell) the cells from inside its compartment elude a kind of proteins known as the sugar transporters or carriers to carry the glucose molecules inside the cells. This will happen only in the presence of insulin attached well to the cell receptors without any resistance. The cells metabolize the glucose to produce energy and other needed molecules and the remaining will be converted into Glycogen and Fat for storage into muscles and adipose tissues.

Excretion

Insulin after consumption by the tissues as a remaining portion cannot either circulate in the system or re-enter into its original place of production as it is harmful if it remains in the body hence the body eliminates it as unchanged in the urine by kidneys.

Oral Anti Diabetics-A Brief

1.Sulphonylureas:-Chlorpropamide, a first-generation drug (Diabinese);
                                Glibenclamide, a first-generation drug (Dionil)                   

                               Tolbutamide, a first-generation drug (Orinase)

                                Glyburide, a second-generation drug(Micronase)

                                Glipizide, a second-generation drug, high potent (Glucotrol)

                                Glimepiride, a second-generation drug, high potent (Amaryl)

 MECHANISM: They stimulate the release of endogenous insulin from the pancreas  and increase the binding strength of insulin to its target receptors 

                                                        TOXICITY:1.Hypoglycemia a condition in which the blood glucose level is abnormally low due to an overdose

2.Gastro-intestinal distress

3.Pruritus

4.Nausea

5.Agranulocytosis and aplastic anemia (rare)
 Metabolism and Excretion: These agents are metabolized in the liver and excreted in the urine

2.Biguanides

1.Metformin (Glucophage) and

2.Phenformin

              Mechanism: It is assumed as glycolysis in the peripheral tissues and reduces hepatic gluconeogenesis. Metformin is contraindicated in Liver and Kidney diseases, in Cardiac arrest, and chronic hypoxic lung disease. It is also advised to stop metformin prior to the radiological procedure involving the usage of iv iodinated contras medium to avoid possible renal failure.                                        
 Excretion:
 Metformin is excreted unchanged by kidneys without metabolized in the liver               Toxicity:1. Lactic acid elevation in the blood as is excretion is blocked                                                       2.Diarrhea, nausea, and stomach upset.

                                                                   3.Decreased absorption of Vit.B-12, and Folic acid in long time use

3.Alpha Glucosidase Inhibitors:  1.Acarbose (Glucophage):Mechanism: This drug delays the absorption of glucose from the GI tract.

                                                  Metabolism and Excretion: Acarbose is metabolized within the GI tract by intestinal bacteria and digestive enzymes and excreted in stools and some amount which entered in the system may be excreted unchanged by kidneys in the urine. 

                                                  Toxicity: GI distress, bloating and diarrhea
                                        

4.Thiazolidinediones:

The use of these groups is now under consideration as rosiglitazone is withdrawn from the market for its serious hepatitis side effects. The other members of this group such as pioglitazone(Actos), rosiglitazone(Avandia ) are still used in many countries.

Vidaglyptin 

It is a Dipeptidyl peptidase (DPP) inhibitor class of medicine. It inhibits the enzyme and thereby promote the action of Glucagon-Like Peptidase and Gastric Inhibitory Polypeptide(GPP) and thereby promoting the insulin secretion in the pancreas

 In the news:-Energy Healing May Help Treat Type-1 Diabetes Patients, Says A New Study

Arpita Bose | Mar 3, 2016, 07.41 AM IST

At a time when doctors talk of a diabetic epidemic in society, a well-known diabetologist in Chennai has argued that the disease is over-diagnosed. Questioning the use of medication, Dr. C V Krishnaswami has also advocated the use of alternative healing in diabetes treatment -methods that other doctors, asking for evidence, often dismiss as unproven pseudo-science.

Now a new study by TAG-VHS Diabetes Research Centre shows a form of "metaphysical energy therapy" that may help those afflicted with Type 1 diabetes come out of their life-long dependence on medicines. The medical paper published in the Journal of Diabetes Mellitus (JDM), a peer-reviewed medical journal in the US, is a major step forward in juvenile diabetes research, says Dr. Krishnaswami, the lead author of the paper. "This is a paradigm shift in research where we have introduced the concept of energy medicine and used it to heal imbalances in the body. In our study we found that the use of this alternate form of medicine helped people reduce their dose of insulin and one went off it completely," he adds. Dr. Krishnaswami, however, says the study is at its nascent stage and requires in-depth analysis before a treatment procedure can be recommended.

Type 1 diabetes usually occurs in children below the age of 15 years in which the body's immune system attacks a part of its own pancreas, mistaking the insulin-producing cells in the pancreas as foreign, and destroys them. The DAMM therapy that was tested on 15 people, with recent and longstanding insulin-dependent diabetes mellitus showed significantly improvement in fasting C-peptide levels in six cases. "In this study, with this new mode of treatment, we could find out the improvement in fasting C-peptide levels and weight of the subjects, with minimum settings of DAMM Therapy and medium dosage of insulin intake," says Dr. Krishnaswami.

Therapy is said to infuse and transfer healing energy from the environment (cosmos) through the therapist, to the patient using acupuncture.

Lack of access to expensive insulin, limited health professional expertise concerning childhood diabetes, and extreme poverty can result in misdiagnosis of the disease which may lead to loss of vision, end-stage renal failure, and severe neuropathy in the 20s or even earlier. With the advent of this the new study, which reports no apparent side-effects in the treatment, the cost of treatment can be greatly reduced, believes Dr. Krishnaswami. "Though the incidence of Type I diabetes is much lower in India as compared to the western countries, the numbers are still sizeable in our country," he added.

Located inside the VHS campus, TAG-VHS, a 40-bedded hospital, was established in 2011. It uses a range of "non-invasive procedures" based on energy medicine, which Krishnaswami says science is now recognizing.

Gut bacteria could help understand diabetes better

Could the trillions of bacteria in our gut hold the key to understanding why some people get diabetes and also offer a potential cure?

To find out, doctors in India and Denmark are collecting samples of stool from about 900 people in both countries, extracting DNA from it and studying it — to figure out for instance, if Indians have more aggressive gut bacteria leading to insulin resistance, or how diverse the bacteria are, and how they are affecting the health of people.

The study called ‘Microbdiab’— jointly funded by the Danish government and the department of biotechnology, Government of India — is a collaboration between three organizations in India, including Dr. Mohan’s Diabetes Specialties Centre, as well as the University of Copenhagen.

The stool samples are from people who are pre-diabetic, diabetic, and normal — 450 samples in each country.

Oluf Pedersen, professor of molecular metabolism and metabolic genetics, faculty of health and medical sciences, University of Copenhagen, Denmark, says, “Gut bacteria produce thousands of compounds that enter the bloodstream, are circulated to all organs, and have an impact. Studies have shown they impact the brain too. They can cause diabetes or lead to obesity.

Different disorders

They have an enormous capacity for inducing different disorders. Is there a role for gut bacteria in the development of pre-diabetes and type 2 diabetes and is there a universal gut bacteria that are contributing to causing diabetes worldwide — these are some of the questions we are studying,” said Prof. Pedersen.

Prof. Pedersen was presented the 25th DMDSC Gold Medal Oration Award on Wednesday. Research has indicated that certain gut bacteria are linked to type 2 diabetes, but whether they are innocent bystanders or part of the causation is yet to be explored, he said.

The Microdiab study began a year ago, and is expected to come up with findings in about six months or so, said R. M. Anjana, joint managing director of the Centre.

Indians could have less good bacteria or less diverse bacteria or more bad bacteria, said V. Mohan, chairman of the Centre.

The Indian diet could be a contributing factor, as diet affects gut bacteria.

Prof. Pedersen, in previous research, has been able to show that those who have more diverse gut bacteria are protected from various diseases like type 2 diabetes and obesity, he said.

Eventually, the goal would be to develop prebiotics or probiotics, to help good bacteria flourish so as to prevent type 2 diabetes, said Prof. Pedersen.

His research has shown that even monozygotic twins have different gut bacteria.

Elaborating on his experiments, he said injecting the gut bacteria of an obese mouse into a germ-free mouse could make the latter obese.

Injecting a lean mouse’s gut bacteria into a germ-free mouse led to the mouse remaining lean — showing that gut bacteria could influence obesity

900 stool samples will be taken from people who are pre-diabetic, diabetic and normal in India and Denmark

 

                                 

PARACETAMOL

Post-2         PARACETAMOL ASPIRIN AND OTHER NSAIDs                 Pharmacology,Toxicology,& Therapy

1)

(a) Paracetamol

Paracetamol the commonly used drug as a painkiller is available in all retail pharmacies as a OTC medicines by various trade names like Tylenol,Dolo etc.The medicine is available as Tablets,Liquid orals and injecions.Although it is not as strong as Aspirin and other NSAIDs it is prefered by physicians for pains and fever as it is mostly stomach friendly.Paracetamol is the drug of choice for women to get relieved from painfull periods.The above video describes the functions and toxicity of Paracetamol in lecture.

The following video would describe a detailed view of this drug's toxic effect.

After Paracetamol is administered orally it is readily absorbed into the body system but mostly metabolized  in  liver into the toxic N-acetyl-p-quinone which is necrotic to the liver muscles if attacked  directly. But thank God it may not happen as if there is sufficient presence of the enzyme Glutathione in Liver.The sulfydryl group of the enzyme would neutralise the toxic metabolite of Paracetamol before it get access to the hepatic muscles.But frequent and careless administration especially to children as it is available in palatable flavoured syrups and may be in some occations prescribed by some paediatricians would lead to disaster.

Please see the following video:

CHEMISTRY

About 100 years ago a chemical known as Acetanilide is included in the patients prescription which after administration converted by the body into paracetamol and aniline.While paracetamol works as analgesic aniline on the other hand very toxic.To avoid this the chemists later on worked hardly and modified acetanilide into N-acetyl-para-aminophenol known as Acetaminophen in U.S.A and Paracetamol in other parts of the world.

Paracetamol in its chemical structure is resembling that of Aspirin and hence recognised by the same enzymes which are responsible for the synthesis of Prostaglandin.Hence paracetamol too is used as analgesic like aspirin but unlike aspirin which is an acid paracetamol is basic and hence it is harmless to stomach
Pharmacokineics

Paracettamol once absorbed is meabolised mainly in liver and to a lesser exent intestine.Paraceamol in therapeuic doses is metabolised to a major exend to phrmacologically inactive glucouranide and sulfide canjugates and to a minor extend to highly active NAPQI (N-amino-p-quinone) which is mostly causing hepato toxicity and is detoxified by the precence of a protecive enzyme Glutathione in the Liver.Glutathione combines wih NAPQI wih its sufidryl bond to form a bondage and ultimately excreted in urine as cysteine and mercapturic acid conjugates.

Pharmacodynamics

Paracetamol has a central analgesic effect that is mediated through activation of descending serotonergic pathways. Debate exists about its primary site of action, which may be inhibition of prostaglandin (PG) synthesis or through an active metabolite influencing cannabinoid receptors. Prostaglandin H₂ synthetase (PGHS) is the enzyme responsible for metabolism of arachidonic acid to the unstable PGH₂. The two major forms of this enzyme are the constitutive PGHS-1 and the inducible PGHS-2. PGHS comprises of two sites: a cyclooxygenase (COX) site and a peroxidase (POX) site. The conversion of arachidonic acid to PGG₂ is dependent on a tyrosine-385 radical at the COX site. Formation of a ferryl protoporphyrin IX radical cation from the reducing agent Fe³⁺ at the POX site is essential for conversion of tyrosine-385 to its radical form. Paracetamol acts as a reducing cosubstrate on the POX site and lessens availability of the ferryl protoporphyrin IX radical cation. This effect can be reduced in the presence of hydroperoxide-generating lipoxygenase enzymes within the cell (peroxide tone) or by swamping the POX site with substrate such as PGG₂. Peroxide tone and swamping explain lack of peripheral analgesic effect, platelet effect, and anti-inflammatory effect by paracetamol. Alternatively, paracetamol effects may be mediated by an active metabolite (p-aminophenol). p-Aminophenol is conjugated with arachidonic acid by fatty acid amide hydrolase to form AM404. AM404 exerts effect through cannabinoid receptors. It may also work through PGHS, particularly in areas of the brain with high concentrations of fatty acid amide hydrolase.

(Thanks to http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9592.2008.02764.x/full)

Also see the following video:-

For further details go to the foiiowing links:-http://fileam.com/file/0558l56

http://okayfiles.com/file/0558l63http://okayfiles.com/file/0558l63

(b) Aspirin

Acetyl salicylic acid as it is generically known by a chemist is made into familiar and well branded as ASPIRIN commercially by Bayer company.But it is now world wide manufactured and distribued by various companies by various commercial names.
To have a further full details of NSAIDs please click here the downloadable link to download into your computer for your reference

Diclofenac

http://reliabledownloads.org/file/05595969