SATURATED FATS INCREASE HEALTH?

ARE MEAT,EGGS,BUTTER,CHEESE-HARMLESS?

The answer is yes, says a recent study at the KG Jabsen Center For Diabetes Research at the University of Bergen
The saturated fats intake rather increases the good cholesterol and not increases the risk of heart attack, the researchers say.
The above concept is totally against the old concept of the intake of saturated fats such as red meat, butter and cheese increase the risk of heart attack and stroke.
In the new Norwegian Fat Intervention study (FATFUNC) published in The American Journal of Clinical Nutrition study leader asst prof. Simon Nitter Dankel et al have overturned and questioned the older dietary concept that taking saturated fat is unhealthy for the population which dominated the medical literature for more than 50 years.
The notion of reducing saturated fat intake to keep the body weight in control and to prevent many chronic illnesses such as heart attack, blood pressure, and many diseases. But the scientists and many health organizations however contrasted with this theory with recent studies.
The American Heart Association (AHA) goes with the government warnings and echo that consuming too much-saturated fat may cause heart attack and other problems.
But The Academy of Nutrition and Dietetics however recommend de-emphasizing the role of saturated fat in causing heart problems as there is no established link between the two.
The majority of the foods containing saturated fat comes from animal sources and dairy products.
The AHA recommends reducing the intake of these foods based on the strong science they believe behind the old concept.
Daniel and his colleges tested the harmful effects of saturated fat on 38 men with abdominal obesity. The participants were divided into two groups. Group A was given a diet rich of high fat with low carbohydrate and group B was given a diet rich of low fat and high carbohydrate for 12 weeks.
The researchers measured the fat mass in the abdomen and also assessed cardiovascular risk factors.
They found the result was negative towards the current theory of the group which was with the diet of high fat and low carbohydrate diet should be at higher risk of getting cardiovascular problems than the other group.
However that was not the case, there was no difference between the groups. 
"The very high intake of total and saturated fat did not increase the calculated risk of cardiovascular disease", the researchers said.
On contrary the participants under high saturated fat diet shown substantial improvements in several cardiometabolic risk factors such as ectopic fat storage (Fat deposits around the organs in the abdominal cavity such as liver and pancreas, skeletal muscle, heart and mainly as triglycerides with very little adipocytes), blood pressure, blood lipids, insulin, and blood sugar.

The Overriding Principle

Finally from the study, we could understand it is not the quantity of saturated fat but it is the quality of the saturated fat that may affect our health.

 

 

ERYTHROBLASTOSIS OR HEMOLYTIC ANEMIA

ERYTHROBLASTOSIS FETALIS

 

This is a condition in which the red blood cells are destroyed by an autoimmune system of our body and thereby cause oxygen depletion and tissue death. The condition is very serious and fatal.

Rh factor is a kind of an inherited protein usually present on the surface of the red cells(RBC). People whose RBC contains Rh factor are considered to be Rh-positive. On the contrary those whose RBC not contains Rh factor are considered to be Rh-negative.

If the mother is Rh-negative and the father is Rh-positive then the child would be mostly Rh-positive. If this is the case then the pregnancy will be risky for both mother and child. During such pregnancy if any opportunity occurred for mixing the mother and baby's blood on either side then it is fatal and risky of getting erythroblastosis by any of them or both.

OPPORTUNITIES

1. During delivery when the placenta detaches from the uterus wall.

2.Pregnancy with heavy bleeding

3.Manual rotation of a breech baby

4.Miscarriage (premature delivery or spontaneous abortion)

5.Ectopic pregnancy(PREGNANCY OUTSIDE WOMB)

6.Abortion

7.Traumas, or a sudden fall.

8.Invasive prenatal tests such as amniocentesis or chorionic villus sampling.

Dangerous Rh sensitization occurs in the mother during chorionic villus sampling. The Rh-negative mother is at risk by mixing her baby's potentially Rh-positive blood with her own.

As a result the mother's body immune system will recognize in future any blood entry of the Rh-positive factor as a foreign body and will attack them. The antibodies produced by the mother may pass into the fetus also and causes the destruction of its RBCs.The result is the death of a fetus or illness due to erythroblastosis and abortion.

The Rh-positive contamination can occur due to careless uses of contaminated injection needles, and blood transfusion.

Erythroblastosis may not occur due to the difference in blood groups.

The fetus may be born with defective blood or illness. The RBCs of the fetal blood are destroyed. They lost their oxygen-carrying function. Severe anemia will stimulate the liver, spleen, and bone marrow to produce more RBC. This may cause organ damage. Excess formation of bilirubin as a byproduct of RBC damage may cause jaundice and the baby will look yellow in color.

Symptoms

1.Yellowish amniotic fluid (The fluid-filled in the pregnant womb) due to excess bilirubin seen on an amniocentesis test

2.An enlarged liver, spleen or heart

3. Fluid builds up in the abdomen, lungs, and scalp can be recognized by an ultrasound scan test.

Newborns may bear with the following symptoms

1.Pale skin

2.Yellow amniotic fluid, umbilical cord, skin, or eyes either at birth or within 24 to 36 hours after delivery.

3.Organs such as liver or spleen enlargement

4.Breathing difficulties due to full body fluid build-ups.Heart failure. The condition is known as Hydrops Fatalis

Complications

1.Mild to severe anemia

2.Jaundice

3.Organ enlargement

4. Kernicterus:-Excess bilirubin build up in the brain causes deafness, seizures, brain damages, and death.

Diagnosis and Treatments

1. A test for Rhesus or Rh factor may be helpful to diagnose and treat the problem.

An antibody screening test in the first semester, followed by a repeat test after 28 weeks of gestation.

This may reveal a clear knowledge about the presence of Rh incompatibility during pregnancy.

2. Testing the fetus include ultrasound test, amniocentesis, fetal middle cerebral artery blood flow measurement, and fetal umbilical cord blood testing.

After birth in the newborn tests for hemolytic anemia must be carried out.

1.Test for blood group and Rh factor

2.RBC count

3.Test for antibodies and bilirubin levels.

The treatments include fetal blood transfusion and delivery of the baby between 32 to 37th week of gestation.

Treatments of the newborn should be carried out with the following conditions:-

1.Blood transfusion

2.Intravenous fluids

3.Management of breathing difficulties

4.Use of Intra Venous Immuno Globin. The use of IVIG antibody treatment is to reduce the RBC destruction and to control bilirubin raise.

Some times exchange transfusions are carried out by replacing a portion of the newborn's blood in order to increase RBC count and to minimize the bilirubin level.

Prevention

The Rh sensitization can be prevented by giving the medication  Rh immunoglobin (RhIg) also known as RhoGAM before women become sensitized.

This is medication helps the mother not develop destructive antibodies.

But this medicine may not helpful to those women who have been already sensitized

Hence this medicine can be helpful only to those women who are not yet sensitized but at the risk of sensitization.RhoGAM can be given as follows:

1.After 28th week of gestation

2.72 hours following delivery

3. Within 72 hours of miscarriage, abortion, or ectopic pregnancy.

4.Following an invasive prenatal test such as amniocentesis, and chorionic villus sampling.

5. Following vaginal bleeding, if any 

If a woman carries beyond 40 weeks of gestation an additional dose of RhoGAM is recommended.

 

NEWS UPDATE:COGNITIVE EFFECTS OF PD PATIENTS ON POSTURES

Standing up may unmask cognitive deficits in patients with Parkinson's

Adapted Media Release

Published: Thursday 1 December 2016

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In a new study published online in the journal Neurology, a research team led by neurologists at Beth Israel Deaconess Medical Center (BIDMC) and neuropsychologists at Boston University has shown that when patients with Parkinson's disease experience a drop in blood pressure upon standing up - a condition known as orthostatic hypotension (OH) - they exhibit significant cognitive deficits. These deficits reverse when they lie down and their blood pressure returns to normal.
These cognitive impairments may go unnoticed by physicians assessing patients with Parkinson's who are lying down or seated, and could lead to difficulty in daily activities performed while standing and walking, such as tracking conversations, counting change and interpreting traffic signals.
"Cognitive impairment is a common symptom of Parkinson's disease," said co-senior author Roy Freeman, MD, director of the Center for Autonomic and Peripheral Nerve Disorders at BIDMC and a professor of neurology at Harvard Medical School (HMS). "In this study, we demonstrated that the upright posture in patients with Parkinson's disease exacerbated cognitive deficits, and that this effect is transient and reversible. Based on these results, we encourage clinicians to include cognitive testing in a variety of postures in their assessments of patients."
Marked by characteristic tremor, rigidity, and slowness of movement, Parkinson's disease (PD) is a progressive degeneration of parts of the nervous system. It affects many aspects of movement and can cause a masklike, expressionless face, rigid limbs, and problems with walking and posture. PD is also associated with cognitive defects attributed to breakdowns in connectivity between regions of the brain. Up to 50 percent of people with Parkinson's disease may also have orthostatic hypotension.
In a previous study, Freeman and colleagues demonstrated that orthostatic hypotension is linked to reversible cognitive impairment in patients with a rare neurological disorder called autoimmune autonomic ganglionopathy. In this new study of the far more prevalent Parkinson's disease, the researchers investigated whether OH is linked to reversible cognitive deficits in patients with PD as well.
Freeman and colleagues including lead author Justin Centi and co-senior author Alice Cronin-Golomb, Ph.D., director of the Vision and Cognition Laboratory and Center for Clinical Biopsychology and a professor of psychological and brain sciences at Boston University divided 55 volunteers into three study groups: 18 patients with both PD and OH, 19 patients with PD but without OH, and 18 control participants with neither PD nor OH. All participants were given a series of cognitive tests, with the tests administered while supine and again while tilted to 60 degrees. Researchers measured and recorded the participants' blood pressure before and during each round of cognitive testing to ensure that participants were never at risk for fainting.
"As we suspected, people with both Parkinson's disease and orthostatic hypotension showed posture-related impairments when upright relative to supine on nearly all measures of cognition," said Centi, who noted that study participants with Parkinson's disease without orthostatic hypotension demonstrated deficits on only two cognitive tests. There was no difference between upright and supine scores for the control group.
When the three groups' relative performances were compared to each other, postural changes had no significant impact on participants with PD but without OH, compared to the control group. However, Participants with PD and OH were far more susceptible to posture-related impairment on several tests, including those that measured math skills, the ability to produce words easily, keeping the information in mind while working on it, paying sufficient attention so that later memory is efficient and searching for items quickly and accurately.
"Essentially all neuropsychological tests are given to patients in the seated position in the clinic as well as during most research studies - with the exception of imaging studies in which the patient is lying down," said Cronin-Golomb. "The cognitive performance that we see in those patients with Parkinson's disease who are tested when seated or lying down, in fact, may underestimate their cognitive problems in real life when they are standing up and going about their business of daily activities. Also, the patterns of brain activity that we see on imaging when they are lying down may not be the patterns that the brain produces during normal upright activity."
Cognitive deficits in PD result, at least in part, from neurodegeneration, the authors explained. But transient blood pressure changes when upright may indeed play a contributing role. Clinical providers might miss an important target for intervention when not considering OH as a contributor to cognitive impairment.
This work was funded by grants from the National Institutes of Health, National Institute of Neurological Disorders and Stroke (R01NS067128) and support from a Ruth L. Kirschstein National Research Service Award (F31NS074801).
Article: Effects of orthostatic hypotension on cognition in Parkinson's disease, Justin Centi, Roy Freeman, Christopher H. Gibbons, Sandy Neargarder, Alexander O. Canova, & Alice Cronin-Golomb, Neurology, DOI: 10.1212/WNL.0000000000003452, published online 30 November 2016.

FRANKINCENSE OIL-FACTS

FRANKINCENSE OIL-REAL FACTS

There are numerous studies have been conducted with the essential oil frankincense which is the major extract of Boswellia Tree.

There is a Biblical concept about the oil that some wise men gifted it to Jesus as it has numerous medicinal values.

The oil is called as Suva in Hindi and kumanjam (குமஞ்சம் ) in Tamil. There are many studies have been carried out with this oil and found that many of its medicinal benefits such as anti-inflammatory, and anti-cancer effects are due to its content known as Boswellic Acid.

Boswellic acid is found to have the effects of stop bleeding, speed up the process of healing, and reduce inflammation.

As several studies have proved that there are links between inflammation and cancer this concept results with a belief that boswellic acid can reduce the incidence of cancer. But further studies are necessary to confirm this. Yet the frankincense oil has not been approved by the FDA as a cancer cure.

The anti-inflammatory effects of frankincense oil can be effectively used to treat Rheumatoid arthritis, Ulcerative colitis, Bronchial asthma, and Crohn's disease(inflammation of the small intestine).

The anti-inflammatory effects of the boswellic acid in frankincense oil are due to the inhibition of an inflammatory enzyme known as 5-lipoxygenase. Also further study has proved that boswellic acid removes free radicals and cytokines and prevents them to produce inflammations at the target cells.

NEWS UPDATE:ELECTRONIC CIGARETTES-PROS AND CONS

E-CIGARETTES-ARE THEY HARMFUL?

In 2003 a Chinese pharmacist has invented a handheld inhaler device to inhale or vape nicotine contain liquid as an alternate for conventional smoking. The device came into the market in 2004. When it was introduced as an alternative to conventional cigarette smoking or stop smoking it rapidly picked up the market. The sales increased exponentially in Europe and America.

The device contains a liquid known as e-cigarette liquid which mainly contains nicotine along with glycerine, propylene glycol and other flavouring agents.

But unfortunately, recent studies have proved that vaping(inhaling) nicotine is as harmful as or more harmful than conventional smoking.

These vaping cigarettes have been found that they make the oral and buccal areas more prone to be damaged by gum diseases and oral cancer. These e-cigarettes cause more damages to mouth cells than tobacco smoking.

The e-cigarettes are handheld battery-operated devices that contain a heating device a cartridge full of liquid which can vaporize while the person puff it and the vapour is inhaled. The liquid contains nicotine as equal to the tobacco.

It is found that the menthol flavoured e-cigarette nicotine causes more damages than the non-flavoured conventional cigarettes.

 

NEWS UPDATE:CONTROLLED GLUCOSE DELIVERY BENIFITS DIABETICS

TYPE 2 DIABETES AND GLUCOSE

Type-2 diabetes is the condition in which the blood glucose level is elevated due to insufficient secretion of insulin from the pancreatic beta isle cells.

A recent study has revealed sweet news that administering controlled pulses of glucose has the power to restore normal insulin production and prevent the development of type-2 diabetes.

The study has been conducted by Dr.Joseph McKenna, from Florida State University and colleagues, and published in the journal PLOS Computational Biology.

We all know that insulin is secreted by the Langerhans Islets(beta islets) of the pancreas. For a full study of diabetes please refer the post-1 in this blog.

In healthy individuals, beta islets release insulin in a pulsatile manner whenever glucose enters into the blood. Glucose enters the system with two sources. The first source is food that is absorbed from the digestive system. Another source is glucose that is generated and secreted from the liver which is endogenous.

The pulses of insulin released from the islets of pancreas restrict the amount of glucose released from the liver as well as regulate the absorption of glucose by our body tissues.

However, in people with diabetes, this regulation is impaired and the islets of the pancreas are no more responding to glucose secretion either from liver or from the digestive system. This eventually leads to hyperglycemia an elevated glucose level in the blood which is known as diabetes mellitus.
High levels of glucose or splash entry of glucose may cause over-stimulation of the islets and may cause damages or blunt their sensitivity.
A newer study has revealed a controlled entry of glucose into the system may repair the islets of the pancreas and can make them more responsive to secret sufficient insulin.
A daily intake of 15gms of glucose may be healthy for a type-2 diabetic patient.

ROLE OF mRNA IN DM

A new study in mice has been revealed that micro RNA may be useful in treating type-2 diabetes in humans. A report from Xiaolin Lin of Southern Medical University, Guangzhou, China has been revealed in PLOS Genetics.

The study found that the serum of type 2 diabetic patients had lower levels of mRNA (miR-155) than healthy people. This suggests that this miR-155 might be involved in blood sugar control and diabetes.

The study shows that the miR-155 dampening some molecules which are interfering with the ability of insulin to respond to the higher glucose levels. Hence it is concluded that a lower level of this type of mRNA causes unresponsiveness of insulin to sugar level.

CONCEPTS OF PHARMACODYNAMICS

PHARMACODYNAMICS-AN OUTLINE

It is very interesting to know about the drug which has been taken into our body how it acts against our body's physiology.

While pharmacokinetics is described in simple terms as the body vs the drug, pharmacodynamics on the contrary means simply the opposite term the drug vs. the body.

The concepts of pharmacodynamics include the theories of receptor reactions, mechanisms of therapeutic and toxic actions, and dose-response relationships.

RECEPTOR REACTIONS

Receptors are macro-molecules typically made out of proteins that interact with either an endogenous substance or an exogenous substance to mediate a pharmacological or physiological effect.
Receptors are functioning by ligand(an endogenous or exogenous substance) and activation of an effector messenger system
Effectors transduce a stimulus produced as a result of drug-receptor interactions into a physiologic effect. There are four types of effector mechanisms:-
1.Transmembrane
Some endogenous ligands such as insulin cannot enter inside the cell instead they interact with the outer component of its receptor present on the cell. This interaction produces a stimulus that is transduced into the inner component of the receptor present inside the cell that contains the enzyme tyrosine kinase to produce a physiologic effect that is the entry of glucose into the cell.
2.Ligand-Gated Ion Channels
When an active drug specialized for these kinds of receptors binds to them that makes a series of conductance of effects to open the ion gates situated by the sides of the receptors to produce powerful ion influxes and effluxes.
The best examples are benzodiazepines that make Cl- ion influx and acetylcholine that make Na+ ion influx.
3.Intracellular
In these types the ligands or substances react with the cellular receptors to form receptor complexes and enter inside the cell and interact directly on the DNA which causes changes in gene expressions. (e.g.)Thyroxine and steroid hormones.
4.Second Messenger Systems
Drugs bind to receptors that cause the activation of a second messenger system that involves G-proteins.
The second messengers the G-proteins such as Guanosine Tri Phosphates (GTP) and Guonosine Di Phosphates allow cell surface receptor signals to be converted and amplified into a physiologic cellular response.
There are three types of second messenger systems that follow below:-
1.Cyclic Guanosine Monophosphate(cGMP)
These are one of the major second messenger systems responsible for many physiologic cell responses such as ion channel conductance, glycogenolysis, and cellular apoptosis a process of older cell deaths by DNA defragmentation.
cGMP also causes vasodilation and increased blood flow. This action is well demonstrated by some erectile stimulating drugs like sildenafil(Viagra) which causes accumulation of cGMP to dilate the blood vessels of the penis to get more blood to flow into it for a perfect erection.
cGMP is produced by the enzyme guanylyl cyclase from GTP and is reconverted back into GTP by a cGMP specific Phospho Di Esterase(PDE).
2.cyclic Adenosine Mono Phosphate(cAMP)
the cAMP is a second messenger that is produced by adenylyl cyclase from ATP(adenosine triphosphate).cAMP involves many physiological effects such as glucose regulation.
3.Inositol Tri Phosphate (IP3)
This is produced by the enzyme Phospholipase-C. It is mostly used in signal transduction, and lipid signaling in biological cells.

Mechanism Of Therapeutic and Toxic Action

These mechanisms involve a drug binding to a receptor in order to stimulate or inhibit it.

A drug that binds with a receptor in order to stimulate and produce a maximum 100% biological effect is known as a Full Agonist.

A drug that binds with a  receptor in order to inhibit and block the biological effects is known as an Antagonist.
A drug that does not stimulate a receptor to a maximum extent and not to produce a 100% biological effect no matter whatever its concentration is known as Partial Agonist. 
If an antagonist binds to the same receptor site of an agonist competitively and reversibly is known as Competitive Antagonist.
If an antagonist binds to the different receptor sites of an agonist non competitively and irreversibly is known as Noncompetitive Antagonist.
A competitive antagonist can be overcome by increasing the concentration of the agonist. The high concentration of the agonist can replace the reversibly bound antagonist from the receptor site.
A non-competitive antagonist cannot be overcome by increasing the concentration of the agonist.
A drug's maximum efficacy is reduced thus by the presence of a non-competitive antagonist.

Dose-Responce Relations

Efficacy is defined as the ability of a drug to produce the expected biological response. A drug is said to be more efficacious if it produces the required biological response at a maximum level independent of the dosage quantity given.

On the contrary potency is defined as the minimum quantity of the drug to produce the required biological response. A drug is more potent if it produces the required biological response with a minimum quantity of dosage.

In simple terms, efficacy is a qualitative measurement whereas potency is a quantitative measurement

Examples can be described as follows:-

If two drugs A and be B both are claimed to reduce a person's heart rate by 35% and then we can say both are equally efficacious

If drug A requires 30mg to produce a heart rate effect of 35% while drug B requires 50mg to produce the same effect then drug A is said to be more potent than drug B.

The concentration of the drug required to occupy 50% of the receptor is known as the dissociation constant (Kd)

The concentration of the drug required to produce 50% of the maximum response is known as EC50.

 

 

 

FUNDAMENTALS OF PHARMACOKINETICS-PART-4

PHARMACOKINETICS-4

EXCRETION

The process by which a drug or its metabolite is eliminated from the body. It is the final and last part of the phenomenon of pharmacokinetics.

Excretion and Secretions are two different entirely opposite actions of the body on a drug. Excretion is a passive movement of the drug according to the concentration and pressure gradient towards its port of elimination.

Secretion needs special oxidation-reduction energy which the body gets from some oxidation-reduction process to move the drug against its concentration and pressure gradient from one compartment to another compartment. The best example is the tubular secretions of some reabsorbed blood contents like sodium, potassium, and chloride ions back into the renal tubules.

The major routes of excretions are,

1.The Kidneys by urine

2.Fecal or stools by colon and rectum

3.Lungs by respiration

4.Breast Milk 

5.Skin by sweat.

PRINCIPLES OF PHARMACOKINETICS-PART-3

PHARMACOKINETICS-3

METABOLISM

In this post we deal with the third principle of the body's action on the drug administered into it, which is Metabolism or Biotransformation.

Metabolism is the process by which the drug which is a foreign and unwanted substance to the body is biologically converted into another form either to make it inactive, or less toxic and to be eliminated easily. These processes mostly happen in the liver. But unfortunately liver may sometimes biotransform some drugs into more active and highly toxic metabolites unintentionally.

Lipophilic, fat-soluble nonpolar molecules are converted into hydrophilic, water-soluble polar molecules in order to eliminate them from the body.

Metabolism is conducted by two phases of reactions such as Phase-I and Phase-II.

In Phase-I reaction lipophilic, fat-soluble,non-polar molecules are converted into hydrophilic, water-soluble polar molecules by introducing or unmasking a polar group in it. These reactions are occurred mostly by oxidation, reduction(mostly by dehydrogenation, or deprotonation, or removal of a positive charge), and hydrolysis(addition of a water molecule or hydro group).

On the contrary in Phase-II conjugative reaction, conjugation between a functional group of the parent drug and a substrate occurred by a strong covalent bond formation.

Usually the substrate is, Glucuronate(the most common substrate), Acetic Acid, Glutathione(as with the toxic paracetamol metabolite N-acetyl-p-benzoquinone imine in order to make it into inert to save the liver) and sulfate.

Most of the metabolic process occurs in liver but some are in the cellular level. In the tissue, cell metabolism occurs in the endoplasmic reticulum(a cytoplasmic cleft present within the cytoplasm) and in the cytosol.

Factors Affecting Metabolism

Genetic Factors

There are differences between the capacities of metabolizing a drug among individuals. For example, some people are slow acetylation and therefore cannot rapidly inactivate some medicines like isoniazid, procainamide, and hydralazine.

Induction of the Cytochrome P-450 system

Rapid induction of this system increases the rate of metabolism.

and inhibition of this system may block the metabolism of some drugs.

The disease especially of the Liver

Age 

Gender

All metabolic processes are mathematically following the zero-order and first-order reactions.

First Order Kinetics

By this model a constant amount of drug is biotransformed in unit time.

For example 10% of a drug,is eliminated or metabolised in the concentration of 100mg/dL by every 2 hrs,then after 2 hours the concentration will be (100-10) 90mg/dL and after 4 hours (90-9),81mg/dL and so on.

The concentration of the drug is directly proportional to the rate of metabolism in first-order kinetics.

Zero Order Kinetics

The amount of drug elimination is a constant figure independent of is the concentration per unit time.

For example if a drug concenration 100mg/dL and the body can remove 10mg/dL in every 2 hour,then after 2 hour there will be a concentration of (100-10)=90mg/dL;and after 4 hours there will be a concentration of (90-10)=80mg/dL and so on.

Alcohol is metabolized as per the zero kinetics only.

PHARMACOKINETICS-FUNDAMENTALS-PART-2

PHARMACOKINETIC PRINCIPES-2

DISTRIBUTION

In part-1 for this subject in the last post we dealt with the beginning point of the pharmacokinetics-Absorption.

In this part-2 we will see the next aspect after absorption, the Distribution.

The process of Distribution is defined as the process in which the drug leaves the bloodstream into the tissue cells.

There are three biochemical mechanisms by which the process of absorption and distribution proceeds.

Passive Diffusion:-

Passive diffusion is governed by a concentration gradient formed across the area of absorption and distribution, which is a cell membrane of tissue. The concentration gradient pushes the drug from the area of high concentration to the area of low concentration. Many lipophilic non polar ions are absorbed and distributed by passive diffusion and it is the most common mode of drug distribution.

Active Transport

In this way some drugs move against the concentration gradient. For this a special energy is required which is derived from the conversion of Adenosine Tri Phosphate(ATP) to Adenosine Di Phosphate(ADP) by the enzyme ATP-ase. The best example is the movement of [H+]ion across the membrane of the parietal cell of the stomach by the ATP-ase pump to let out.

Transport by Special Carrier

There are some special proteins that help to distribute the drug by bounding up with them.

Factors Affecting Distribution

1.Blood Flow.

Distribution is directly proportional to blood flow similar to absorption.

2.Capillary Permeability.

Capillaries are having various thickness and permeability in its structure at various organs. For example in the brain the cells are arranged very tightly with the capillaries with very veery narrow junctions and distribution is slow as only smaller molecules are permeable through the junction between the cells. Conversely in liver and spleen the cells are not so tightened in arrangements embedding the capillaries and they joined with wider junctions so that large molecules can pass through the capillaries and distribution is high across these organs.

3.Binding with Plasma Proteins

Albumin is the common plasma protein that binds with the drugs and limits their distribution as albumins are large protein molecules difficult to cross the capillaries.

4.Drug Structure

In the drug molecular structure if they are non-polar lipophilic then they are smaller and are more rapidly distributed than the large ionized polar molecules.

 

 

PHARMACOKINETICS-FUNDAMENTALS-PART-1

PRINCIPLES OF PHARMACOKINETICS

Pharmacokinetics is better defined as the action of the body on the drug from its entry point to its exit point.

The actions of the body can be better classified as Absorption, Distribution, Biotransformation(Metabolism)

and Excretion.

Absorption

Absorption can be better explained as the rate at which the drug is moved from its site of administration into the body.

Factors Affecting Absorption

The rate and efficacy of absorption can be affected by the following factors.

1.Route of Administration:-

At the following sequences, the routes affect the absorption

Sublingual<Buccal<Oral<Dermal<Intradermal<Subcutaneous<Intramuscular and other parenteral <Intravenous.

From the above sequences we come to know that the most effective absorption happened at the intravenous route. The drug is 100% absorbed directly into the system by that route.

2.Blood Flow:-

In a highly vascularized area with heavy blood flow such as in small intestine the absorption is more.

3. Surface Area Available:-

The drug absorption is high at higher surface area available.

4.The solubility of a Drug:-

The ratio of the lipophilic to hydrophilic (Partition Coefficient) will decide whether the drug can permeate into a cell membrane. In short a drug that has higher lipophilic moiety will easily pass into the cell membrane to be absorbed.

5.Drug-Drug Interactions:-

When given in combination they may interact which can determine whether to inhibit or enhance the absorption

6.Hydrogen Ion Concentration:

H-ion concentration is usually measured by the negative logarithmic values in the pH scale. The pH of the drug which is acidic or alkaline may affect the absorption.

Many drugs are either weak acids or weak bases and their ionization is partial. Acidic drugs are uncharged when protonated as follows,

                [H+] + [A-] < > [HA] (uncharged)

Basic drugs are charged when protonated as follows

                [B]  + [H+] < > [BH+] (charged)

Generally the uncharged ions are non-polar and lipophilic and can easily pass through the lipid content of the cell membrane. 

Therefore the amount of drugs absorbed depends upon its ratio of charged to uncharged particles which in turn is determined by the ambient pH at the site of absorption and the pKa value which is the negative logarithm of the dissociation constant of the drug.

The fraction of the administered drug available for its biological effect after absorption is known as bioavailability.

The intravenously injected drug has 100% bioavailability as it is completely absorbed into the system.

The first pass hepatic metabolism and all other factors described earlier that affect absorption are also the factors that affect bioavailability.

Routes Of Drug Administration

1.Alimentary canal

2.Parenteral(Injections,infusions etc.etc.)

3.Inhalation

4.Topical (Skin)

5.Transdermal

Types of Alimentary Routes:-

1.Oral

2.Buccal

3.Sublingual

4.Rectal

Types Of Parenteral Routes:-

1.Intravenous

2.Intramuscular

3.Subcutaneous

4.Intradermal

5.Intrathecal

Many pulmonary agents are preferred for administration through inhalation.

Many drugs to be used for local skin applications are preferred by topical routes.

Many sustained-release drugs are used through the trans dermal route. 

 

 

 

NEWS UPDATE-CHOLESTEROL LINKED WITH OSTEOARTHRITIS

OSTEOARTHRITIS AND CHOLESTEROL

Osteoarthritis a painful condition especially at the joints are caused by high cholesterol which triggers mitochondrial oxidative stress within the cartilage and neuronal tissues and ganglia, a result of a new research study.

New research published in the FASEB journal online in animal models found that high cholesterol triggers mitochondrial oxidative stress on cartilage cells causing them to degrade and die leading ultimately to the development of osteoarthritis.

Antioxidants targeting mitochondrial oxidative stress can be a suitable treatment for cholesterol-induced osteoarthritis.

Indira PrasadamPh.D.a researcher from the Institute of Health and Biomedical Innovation, School of Chemistry, Physics, and Mechanical Engineering at the Queensland University of Technology in Brisbane, Australia, said that we have already started working with various dietitians to give proper public education about eating a healthy diet free from bad cholesterols in order to save them from mitochondrial oxidation of cartilage tissues.

In general the research found that bad cholesterols are not only harming the cardiovascular system but their traps extending to extra C.V systems such as neuronal and skeletal systems.

The researches used two sets of animal models for the study. The first model was a mouse model in which an altered gene called ApoE-/- was induced to induce hypercholesteremia.

The other was a rat model that was fed with controlled cholesterol food to produce diet-induced hypercholesteremia and among them some were treated with cholesterol-lowering drugs atorvastatin and some were given with antioxidants. Both the models were subjected to surgery to mimic knee injuries to produce osteoarthritis. Later they found the mouse models with altered genes and high cholesterol were developed rapidly osteoarthritis than those were given with normal controlled diet and those with cholesterol-lowering treatments and those with antioxidants. This because of the high cholesterol which triggers mitochondrial oxidation of bone cartilage cells.

Include antioxidants in our diets are always advisable especially after forty years in order to get rid of the painful osteoarthritis.

NEWS UPDATE-GENETIC THERAPY FOR ALZHEIMER DISEASE

ALZHEIMER'S-A GENETIC APPROACH

A newer treatment method to cure Alzheimer's is tested successfully. The research was published in the journal Proceedings of the National Academy of Sciences.

The research involves a treatment that delivers a virus to a gene in the brain that could be used to resolve early symptoms of Alzheimer's Disease.

Alzheimer's disease is the most common and devastating form of dementia affecting 40 million people worldwide. It involves memory loss, mood changes, confusion, and personality changes. Currently there are no cures for this.

The Centers for Disease Control(CDC) has estimated that nearly 5 million people are suffering from Alzheimer's disease in the United States itself and in 2014 at about 93541 deaths were attributed to this disease. Alzheimer's disease becomes the sixth main cause of death in the U.S.alone.

The research conducted by scientists from the Imperial College of London. They used a modified virus that delivers a gene known as PGC1-alpha to the brain cells of the mice. They found that it cures the development of Alzheimer's Disease.

The virus is called a lentivirus vector and is commonly used in gene therapy.

On the basis of the research they found that the gene stop a protein called amyloid beta-peptide from forming cells.

Amyloid plaques are sticky clumps of protein formed mainly at the cortex and the front lobe, the hippocampus of the brain during the development of Alzheimer's Disease (Ref.Alzheimer's Disease) in this blog. These amyloid plaques are causing the death of the brain cells which leads to Alzheimer's Disease.

Prof.Nicholas Mazarakis co-author of the research study explains how they can modify the way of infection by the lentivirus on the brain cells affected by the amyloid plaques for their own advantage and yield beneficiary effects. They use a modified harmless version of the virus.

The research was already used successfully in Parkinson's Disease.

Alzheimer's is developed by starting from the cortex and slowly spread to the hippocampus. The first damage may occur in 10 to 20 years before the disease becomes outwardly visible.

The cortex of the brain is associated with long term memory, reasoning, thinking, and mood. Damage may result in depression and difficulty figuring out to do familiar tasks.

The hippocampus is associated with learning and conversion of short term memories to long term memories. Hippocampus is instrumental in mental orientation.

Damage in the hippocampus may result in forgetting recent events such as a deal on the very day morning. This the main reason why an Alzheimer patient may forget his usual route such as the way to his house.

EXERCISE HORMONE-BENEFITS DIABETICS AND OBESE

Exercise hormone sheds fat, 'helps people stay slender'

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Written by Hannah Nichols

Published: Sunday 2 October 2016 Published: Sun 2 Oct 2016

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If you are lacking in motivation to exercise this fall, some research led by a University of Florida researcher may inspire you to jump-start your fitness regimen. According to the new study, while exercising, a hormone is released that not only helps the body shed fat, but also prevents it from forming.

More regular exercise produces more irisin, which could help with fat reduction, stronger bones, and better cardiovascular health.

A professor of cell biology and a team at Harvard Medical School discovered the hormone dubbed "irisin" in 2012. They isolated the natural hormone from muscle cells that trigger some of the health-promoting properties of exercise, which, they say, could be developed into novel treatments for diabetes, obesity, and cancer.
In the previous study, the Harvard-affiliated team also found that as irisin levels rise through exercise, the hormone switches on genes that convert white fat into brown fat - the "good" fat. This conversion is beneficial, as brown fat burns off more excess calories than exercise alone.
Dr. Li-Jun Yang, a professor of hematopathology in the Department of Pathology, Immunology and Laboratory Medicine at the University of Florida College of Medicine, directed the new research.
Dr. Yang and colleagues aimed to understand the role of irisin in humans better and increase the knowledge base of how the hormone helps convert calorie-storing white fat cells into energy-burning brown fat cells.
The researchers note that they believe the research to be the first of its kind to explore irisin's effects on human fat tissue and fat cells.
According to the researchers, irisin hormone - which surges when the heart and other muscles are exerted - may also inhibit the formation of fatty tissue.
The study findings, published in the American Journal of Physiology-Endocrinology and Metabolism, confirms previous conclusions that irisin may be a promising target to support people with obesity and type 2 diabetes.
Irisin works via a mechanism that boosts the activity of genes and a protein that is crucial to turning white fat cells into brown fat cells. The researchers also found irisin to have a role in burning fat by significantly increasing the amount of energy used by brown fat cells.
Dr. Yang and the team conducted the research by collecting fat cells donated by 28 participants who had undergone breast reduction surgery. Scientists exposed the fat samples to irisin, and as a result, saw an almost fivefold increase in cells that contain the UCP1 protein - a protein crucial to fat burning.
"We used human fat tissue cultures to prove that irisin has a positive effect by turning white fat into brown fat and that it increases the body's fat-burning ability," says Dr. Yang.

Fat cell formation significantly suppressed by irisin hormone

Among the analyzed fat tissue samples, Dr. Yang and collaborators found that irisin suppresses fat cell formation by reducing the number of mature fat cells by 20-60 percent when compared with the control group.
This finding indicates that the irisin hormone reduces fat storage in the body by hindering the process that turns undifferentiated stem cells into fat cells, while also promoting the stem cells' differentiation into bone-forming cells, the researchers say.
More than two-thirds of U.S adults are considered to be overweight or obese. While there is no single approach to prevent or treat overweight and obesity, an exercise in combination with behavioral treatment and diet can aid weight loss. The knowledge that the body produces small quantities of fat-fighting irisin emphasizes the importance of regular exercise.
Dr. Yang says that while the beneficial effects of irisin could potentially be developed into therapies in the future, the viability of an irisin-based treatment is uncertain and would not happen imminently.

"Instead of waiting for a miracle drug, you can help yourself by changing your lifestyle. Exercise produces more irisin, which has many beneficial effects including fat reduction, stronger bones, and better cardiovascular health."

Dr. Li-Jun Yang

Irisin's role in regulating fat cells sheds light on the way physical activity helps people stay slender, says Dr. Yang. "Irisin can do a lot of things. This is another piece of evidence about the mechanisms that prevent fat buildup and promote the development of strong bones when you exercise," she adds.
This study adds to increasing information regarding irisin's health benefits. Previous studies by Dr. Yang's group found that irisin improves heart function by boosting calcium levels that are critical for heart contractions. They also showed that the hormone reduced arterial plaque buildup in mouse models by preventing inflammatory cells from accumulating, thus reducing atherosclerosis.
Future work for the team will focus on irisin's effect on abdominal fat, which is associated with insulin resistance and high lipid levels.
Read about research that disputes the existence of exercise-induced muscle memory.

Written by Hannah Nichols

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Exercise hormone sheds fat, 'helps people stay slender'

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COFFEE CAN REDUCE WOMEN'S RISK OF DEMENTIA

IS COFFEE A PROPHYLACTIVE TO DEMENTIA?

The answer is delicious yes. Today is International Coffee Day and the tasty way to celebrate the day is by sharing this good news with all our readers.

A new study suggests that older women who drink coffee with two to three cups daily may be at lower risk of having dementia and other cognitive diseases.

Researches have concluded that caffeine a mild stimulant present in coffee has many cognitive benefits.

A study regarding the relationship between coffee drinking habits and improvement of long term memory has been published in The Journal Of Nature Neuroscience in 2014.

The new findings of caffeine's benefit in reducing the risk of getting dementia by women are published in The Journals Of Gerontology, Series-A. Biological Sciences and Medical Sciences.

About 6467 women aged 65 years and older were selected for Women's Health Initiative Memory Study(WHMS) which was funded by National Heart, Lung, and Blood Institute

The lead author of this study Prof.Ira Driscoll, Ph.D., noted that 'the unique about this study is that we had an unprecedented opportunity to examine the relationship between caffeine intake and dementia incidence in a large and well defined, prospectively studied cohort of women'.

Driscoll et al examined the participants of the program study by their caffeine intake as determined through self-consumption of coffee tea and cola.

The researches found that women who consume a minimum of 64mgs of coffee (1 8-ounce cup) are more prone to get dementia than those who consume more than 260mgs of caffeine(2 to 3,8-ounce cups of coffee or 5 to 6, 8-ounce cups of black tea).

The team found this beneficiary factor overriding even after accounting the possible confounding factors such as age, race, body mass index, smoking status, alcohol intake depression hypertension, sleep quality, and history of cardiovascular diseases.

The authors of the study say that they are unable to establish a direct association between caffeine intake and dementia risk reduction nor are they able to generalize the findings to men.

NEWS UPDATE-SMOKING THICKENS HEART WALL

SMOKING AND THE PERICARDIUM

It is observed by the latest research that heavy smoking thicken the wall of the heart, the pericardium, and makes it difficult to pump the blood.

The study was published in the journal Circulation.

Smoking is the major cause of many complications in cardiovascular, pulmonary, and other regions of the body.

It has been established that smoking tobacco leads to an increased risk of heart failure even in a healthy individual.

But the mechanism by which the tobacco smoking damages the heart is not clearly established.

NEWS UPDATE-NEW GENETICAL APPROACH TO DM

A GENE THAT CAUSES DM

Type 2 diabetes the most common type of DM affecting 90% of the people in which either the beta cells of the pancreas are unable to produce insulin or the body cannot utilize or respond to the insulin.

Now a research team from the UK has discovered a gene that causes the destruction of the beta islets of Langerhans that produces insulin that contributes to producing type-2 DM.

By blocking the gene TNFR5 halted the destruction process, a discovery that leads to new hope in the treatments of Type-2 DM.

The research team was lead by Dr.Mark Tuner of the School of Science and Technology, at Nottingham University in the UK.

They say that it is certain that a long time use high fat and high sugar diet can worsen the destruction of beta islet cells in Type-2 DM people with uncleared reasons.

But, now they cleared it after research with a number of genes they found that the gene TNFR-5 had the highest sensitivity to glucose and fatty acids and overexpression of this gene in response to the high fat and sugar diet leads to the development of type 2 DM.

Hence they said blocking this gene halted he destruction according to their Laboratory tests.

NEWS UPDATE-COFFEE AND CAFFEINE

COFFEE AND CAFFEINE

It has been found out that occasional coffee drinking is riskier than regular coffee drinking. A research was carried out with a group of occasional coffee drinkers and another group of regular coffee drinkers.

The result has shown those occasional coffee drinkers because of the deep fluctuation of the concentration of caffeine in their blood are prone to have higher risks of blood pressure and other cardiovascular complications.300 ml of black coffee consumption can elevate blood pressure within two hours and last for several hours. Hence a drink of coffee may affect the blood pressure measurement results if it was consumed just before the B.P. measurements by the occasional drinkers.

Also coffee drinking by occasional drinkers may interfere with their B.P.medications, such as calcium channel blockers.

Research has shown that Felodipine a calcium channel blocker used to reduce the B.P when used along with a cup of coffee has elevated the B.P. instead of reducing it.

These are because in occasional coffee drinkers the concentration of caffeine deeply fluctuates even if they drink the coffee with a two days gap.

After a cup of coffee the caffeine concentration remains in the blood for two days only. Within two days the blood is almost cleaned off most of the caffeine content. Then by another drink of coffee at the end of the second-day caffeine reenter into the blood as a fresh candidate and may have all its effects freshly. Hence a drink of coffee on every alternate day too are considered as occasional drinks and the body cannot tolerate caffeine as with the regular drinkers.

Regular daily drinking of coffee will be tolerated by the body and the maintenance of a fixed concentration of caffeine in the blood may not complicate blood pressure and other cardiovascular irregularities.

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