Obesity can be inherited

New research from the University of Adelaide shows that the sperm of obese fathers could increase the risk of both their children and their grandchildren to inherit obesity.

In laboratory studies, researchers from the University's Robinson Institute have found that molecular signals in the sperm of obese fathers can lead to obesity and diabetes-like symptoms in two generations of offspring, even though the offspring are eating healthily.

The results of the research are published online inThe FASEB Journal.

"A father's diet changes the molecular makeup of the sperm. With obese fathers, the changes in their sperm - in their microRNA molecules - might program the embryo for obesity or metabolic disease later in life," says the lead author of the paper, Dr Tod Fullston, who is an NHMRC Peter Doherty Fellow with the University's Robinson Institute, based in Dr Michelle Lane's Gamete and Embryo Biology Group.

"For female offspring, there is an increased risk of becoming overweight or obese. What we've also found is that there is an increased chance of both male and female offspring developing metabolic disease similar to type 2 diabetes.

"This is the first report of both male and female offspring inheriting a metabolic disease due to their father's obesity," he says.

The study also extended into the second generation of progeny, which showed signs of similar metabolic disorders, including obesity, although it was not as severe as the first generation.

Dr Fullston says even if the obese father does not show any signs of diabetes, metabolic disease similar to diabetes was being seen in two generations of their descendants.

"It's been known for some time that the health of a mother before, during and after pregnancy can impact on her child's health, but the father's health during this period is often overlooked," Dr Fullston says.

"If our laboratory studies are translatable to humans, this could be a new and as yet unexplored intervention window into the epidemic of childhood obesity.

"A focus on the mother's health is extremely important, but we're seeing that the father's health is also important for conception. It's possible that by showing additional attention to diet and exercise in the father, this could have a positive impact on his future children and grandchildren."

RHEOLOGY

Rheology

Study of deformation and flow of matter

A fluid is a substance that deforms continuously under the action of a shearing force.

Intuitively, a fluid flows!

Inquiry into the flow behavior of complex fluids

Complex fluids do not follows Newton's Law or Hooke's Law (of elasticity)

 
Newton and Simple Fluids

Reflected upon the resistance of liquids to a cylinder rotating in a vessel.

Newton (-Stokes) Law

Deformation rate is expected to be proportional to stress and the constant coefficient of proportionality is called viscosity.

The study of simpler fluids have their own well-defined field, called fluid mechanics.

Purely viscous fluid.

"Rheology is the study of the flow of materials that behave in an interesting or unusual manner. Oil and water flow in familiar, normal ways, whereas mayonnaise, peanut butter, chocolate, bread dough, and silly putty flow in complex and unusual ways. In rheology, we study the flows of unusual materials."

"… all normal or Newtonian fluids (air, water, oil, honey) follow the same scientific laws. On the other hand, there are also fluids that do not follow the Newtonian flow laws. These non-Newtonian fluids, for example mayo, paint, molten plastics, foams, clays, and many other fluids, behave in a wide variety of ways. The science of studying these types of unusual materials is called rheology"

Examples of Complex Fluids
Foods
Emulsions (mayonaisse, ice cream)
Foams (ice cream, whipped cream)
Suspensions (mustard, chocolate)
Gels (cheese)
Biofluids
Suspension (blood)
Gel (mucin)
Solutions (spittle)
Personal Care Products
Suspensions (nail polish, face scrubs)
Solutions/Gels (shampoos, conditioners)
Foams (shaving cream)
Electronic and Optical Materials
Liquid Crystals (Monitor displays)
Melts (soldering paste)
Pharmaceuticals
Gels (creams, particle precursors)
Emulsions (creams)
Aerosols (nasal sprays)
Polymers

 
Rheology's Goals

• Establishing the relationship between applied forces and geometrical effects induced by these forces at a point (in a fluid).
  • The mathematical form of this relationship is called the rheological equation of state, or the constitutive equation.
  • The constitutive equations are used to solve macroscopic problems related to continuum mechanics of these materials.
  • Any equation is just a model of physical reality.
    
     

2. Establishing the relationship between rheological properties of material and its molecular structure (composition).

• Related to:
  • Estimating quality of materials
  • Understanding laws of molecular movements
  • Intermolecular interactions
• Interested in what happens inside a point during deformation of the medium.

 
(Material) Structure

More or less well-organized and regularly spaced shapes

Arrangements, organization or intermolecular interactions

Structured Materials – properties change due to the influence of applied of applied forces on the structure of matter

Rheology sometimes is referred to as mechanical spectroscopy.

"Structure Mechanisms" are usually proposed, analogous to reaction mechanisms in reaction kinetics

Structural probes are used to support rheological studies and proposed mechanisms.

Rheological analysis is based on the use of continuum theories
meaning that:

• There is no discontinuity in transition from one geometrical point to another, and the mathematical analysis of infinitesimal quantities can be used; discontinuities appear only at boundaries
• Properties of materials may change in space (due to gradients) but such changes occur gradually

 

• changes are reflected in space dependencies of material properties entering equations of continuum theories

 
Rheological Properties

• Stress
  • Shear stress
  • Normal stress
  • Normal Stress differences
• Viscosity
  • Steady-state (i.e. shear)
  • Extensional
  • Complex
• Viscoelastic Modulus
  • G' – storage modulus
  • G" – loss modulus
• Creep, Compliance, Decay
• Relaxation times
• and many more …

Common Non-Newtonian Behavior

• shear thinning
• shear thickening
• yield stress
• viscoelastic effects
  • Weissenberg effect
  • Fluid memory
  • Die Swell

Shear Thinning and Shear Thickening

shear thinning – tendency of some materials to decrease in viscosity when driven to flow at high shear rates, such as by higher pressure drops.

Shear Thickening

Shear Thickening– tendency of some materials to increase in viscosity when driven to flow at high shear rates

Facts about Kidney Disease

1. The incidence kidney failure (or chronic Kidney disease) has doubled the last 15 years.

2. It is estimated that currently there are over 1 million people worldwide who are alive on dialysis or with a functioning graft.

3. Diabetes is an important cause of kidney failure and diabetes is five times more common in the Asians when compared to the white population

4. Another lifestyle related disorder - hypertension is an important cause of kidney failure and it too has seen a global increase in its incidence. Asians again are twice more prone to develop this condition in comparison to the white population.

5. Almost 66% kidney failure occurs due to hypertension or diabetes.

6. There are approximately 7.85 million people suffering from chronic kidney failure in India.

7. It is estimated that there are between 11 to 30 million people with chronic Kidney disease or other evidence of kidney disease in USA.

8. In the United States the cost of treating patients with renal replacement therapy will be US $28 billion by the year 2013. It is estimated that over 600 000 patients will require treatment.

9. In India 90 % patients suffer from kidney disease are not able to afford the cost of treatment.

10. The crisis of kidney shortage is a global phenomenon and it is worst in Asian countries.

PHARMACEUTICAL SUSPENSIONS

DISPERSE SYSTEM

—The term "Disperse System" refers to a system in which one substance (The Dispersed Phase) is distributed, in discrete units, throughout a second substance (the continuous Phase ).

—

—Each phase can exist in solid, liquid, or gaseous state .

—Suspensions are heterogenous system consisting of 2 phases.

   Definition

Ø   A Pharmaceutical suspension is a  coarse dispersion in which internal

      phase (therapeutically active ingredient)is dispersed uniformly

      throughout the external phase.

ØThe internal phase consisting of insoluble solid particles  

     having a range of size(0.5 to 5 microns) which is  maintained uniformly through out the suspending vehicle with aid of single or combination of suspending agent.

Ø The external phase (suspending medium) is generally
 aqueous in some instance, may be an organic or oily  liquid for non oral use.

The reasons for the formulation of a pharmaceutical suspension:

-- when the drug is insoluble in the delivery vehicle.

–To mask the bitter taste of the drug.

–To increase drug stability.

–To achieve controlled/sustained drug release.

SOME PHARMACEUTICAL SUSPENSIONS

—1. Antacid oral suspensions

—2. Antibacterial oral suspension

—3. Dry powders for oral suspension (antibiotic)

—4. Analgesic oral suspension

—5. Anthelmentic oral suspension

—6. Anticonvulsant oral suspension

—7. Antifungal oral suspension

Classification

Based On General Classes

Ø Oral suspension

     eg: Paracetamol suspension

       antacids, Tetracycline HCl.

Ø  Externally applied suspension

      eg :Calamine lotion.

Ø  Parenteral suspension

eg: Procaine penicillin G

Insulin Zinc Suspension

Based on Proportion of Solid Particles

Ø  Dilute suspension (2 to10%w/v solid)

Eg: cortisone acetate, predinisolone acetate

Ø  Concentrated suspension (50%w/v solid)

Eg: zinc oxide suspension

 Based on Electrokinetic Nature of Solid Particles

Ø Flocculated suspension

Ø Deflocculated suspension

Based on Size of Solid Particles

ØColloidal suspensions (< 1 micron)

-Suspensions having particle sizes of suspended solid less than about 1micron in size are called as colloidal suspensions.

Coarse suspensions (>1 micron)

ØSuspensions having particle sizes of greater than about 1micron in diameter are called as coarse suspensions.

Nano suspensions (10 ng)

Ø Suspensions are the biphasic colloidal dispersions of nanosized drug particles stabilized by surfactants.

ØSize of the drug particles is less than 1mm.

Advantages And Disadvantages

ADVANTAGES

Suspension can improve chemical stability of certain drug.

  E.g. Procaine penicillin G.

ØDrug in suspension exhibits higher rate of bioavailability than other dosage forms.

Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

ØDuration and onset of action can be controlled.

    E.g. Protamine Zinc-Insulin suspension.

ØSuspension can mask the unpleasant/ bitter taste of drug.

    E.g. Chloramphenicol

DISADVANTAGES

ØPhysical stability , sedimentation and compaction can causes 

     problems.

Ø It is bulky sufficient care must be taken during handling and 

    transport.

Ø It is difficult to formulate.

Ø Uniform and accurate dose can not be achieved unless suspension are  packed in unit dosage form.

Applications

Ø  Suspension is usually applicable for drug which is insoluble

     (or )   poorly soluble.

    E.g. Prednisolone suspension

Ø  To prevent degradation of drug or to improve stability of drug.

     E.g. Oxy tetracycline suspension

Ø  To mask the taste of bitter of unpleasant drug.
      E.g. Chloramphenicol  palmitate suspension

Ø  Suspension of drug can be formulated for topical application  

     e.g. Calamine lotion

ØSuspension can be formulated for parentral application in order to

    control rate of drug absorption. E.g. penicillin procaine

Ø Vaccines as a immunizing agent are often formulated as suspension.
     E.g. Cholera vaccine

Ø  X-ray contrast agent are also formulated as suspension .

     eg: Barium sulphate for examination of alimentary tract.

Peptic Ulcer Disease- A review

RECEPTORS

RECEPTORS

 

 

 

 

CONTENTS

1- ENZYME-LINKED RECEPTORS
2- LIGAND GATED ION CHANNELS
3- VOLTAGE GATED ION CHANNELS
4- G PROTEIN COUPLED RECEPTORS
5- NUCLEAR RECEPTOR


 

 

 

 

ENZYME-LINKED RECEPTORS

 

These receptors are themselves enzymatic proteins. The agonist binding site lies on the outer, while the catalytic site lies on the inner face of the plasma membrane. These two domains are interconnected through a single trans- membrane stretch of peptide chain.
Most Enzyme-Linked receptors have tyrosine kinase as the enzyme. e.g. Insulin, epidermal growth factor, platelet derived growth factor & certain interleukins. The intracellular events are triggered by phosphorylation of relevant proteins. The receptor itself gets autophosphorylated on tyrosine residues which promote association of several receptor molecules, organizing the complex signaling mechanisms.

 

LIGAND GATED ION CHANNELS

They regulate the flow of ions across the membranes. Ligand binds and regulates their activity. They are fast acting receptors, respond in sub-milliseconds.
Natural ligands include Ach, Serotonin, GABA & Glutamate.
Neurotransmitter binds to the receptor, altering its concentration to open or close the channel to the flow of Na+, K+, Cl- or Ca++ ions across the membrane.
These receptors mediate neurotransmission, cardiac conduction and muscle contraction.


 


VOLTAGE GATED ION CHANNELS

They transport ions across the membrane and are regulated by the electrical potential difference near the channel. Some are composed in a way that they have a central pore through which ions travel down their electrochemical gradients.
Change in potential induces a conformational change in the channel, it opens admitting the ion influx or efflux to occur across the membrane down the electrochemical gradient.
Example include Na+ and K+ Voltage gated channels
They play role in the generation and propagation of nerve impulse across the membrane.

 


 
G PROTEIN COUPLED RECEPTORS

 
These are a large family of cell membrane receptors which are linked to the effector through one or more GTP-activated proteins.
These receptors comprise a α helical peptide which has seven membrane spanning regions.
The extracellular domain contains a ligand binding area, intracellularly, these are linked to a G protein (Gs,Gq,Gi) having 3 subunits α,β,ϒ, that binds GTP.
Binding of ligand to receptor activates the G protein, which releases GDP & binds GTP.
ADENYLYL CYCLASE (c AMP) PATHWAY
Turned on by Gsà activation of Adenylyl Cyclase àintracellular accumulation of
c AMP à increased Ca++ influx and enzyme activity

 

 
PHOSPHOLIPASE C (IP3-DAG) PATHWAY

Turned on by Gq à activation of Phospholipase C à Generation of IP3 & DAG à

Increased intracellular Ca++ and protein kinase activity

 



NUCLEAR RECEPTOR

 
These receptors work with other proteins to regulate the expression of specific genes.
Ligands include thyroid hormone, heme, cholesterol, Vitamin A & D
Ligand binding to the receptors à translocation from cytoplasm to cell nucleus à binding to nuclear hormone response elementsà resulting in up regulation or down regulation of gene expression
There are 48 known human nuclear receptors, e.g. Thyroid hormone receptor, Retinoic acid receptor, Estrogen receptor

 

Gout

Definition:

Gout is a form of arthritis which is caused by the accumulation of uric acid crystals in joints. In this condition, due to a metabolic dysfunction, there is deposition of uric acid in and around the joints causing severe painfulness, swelling and restricted mobility of the affected joint. 

Gout is a disease that results from an overload of uric acid in the body. This overload of uric acid leads to the formation of tiny crystals of urate that deposit in tissues of the body, especially the joints. When crystals form in the joints, it causes recurring attacks of joint inflammation arthritis. Gout is considered a chronic and progressive disease. Chronic gout can also lead to deposits of hard lumps of uric acid in the tissues, particularly in and around the joints and may cause joint destruction, decreased kidney function, andGout has the unique distinction of being one of the most frequently recorded medical illnesses throughout history. It is often related to an inherited abnormality in the body's ability to process uric acid.

Symptoms:
Gout is an intensely painful condition, which mostly affects only one joint (monoarthritis) at a time, most commonly the big toe. However, Gout may also affect elbows, knees, ankles, wrists or small joints of the hands and feet. The classic history in a patient suffering from Gout is of excruciating and sudden pain, swelling, redness, warmth and stiffness of the joint. Low-grade fever may also be present. The skin overlying the joint can also be swollen, tender and sore if it is touched even lightly. Patients with longstanding hyperuricemia (high levels of uric acid in blood) can have uric acid crystal deposits called tophi in other tissues as well, e.g. the helix of the ear.

Causes of Gout:

Hereditary

Improper function of kidney which results in decreased excretion of urates in urine.

Reaction to alcohol. Reaction to certain drugs, including antibiotics.

Enzyme deficiencies.

Lead poisoning.

Disorder is often associated with an injury or surgical procedure.

Highly proteinous diet.

Unidentified causes—Idiopathic causes.

Starvation—diminished renal excretion of uric acid.

Psoriasis—due to over production of uric acid.

Toxaemia of pregnancy—due to diminished excretion of uric acid. May also occur in some cases of tumors or cancers.

Gout has four distinct stages     

 Asymptomatic: High levels of Uric acid in blood but no joint complaints

Acute phase: Acute complaints described above occur for a brief period

Intercritical phase: There is no pain or swelling of joints in this phase, the patient is relatively symptom-free.

Chronic: Gout attacks may become frequent during this phase and the condition may affect many joints at a time (polyarticular). Tophi formation may also be seen.