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.