disease state this value can exceed upto 3.0 mg/ml. AAG and HSAshare similar values of association constant. similar to Hsaconstitutes a single polypeptide chain of 181 amino acids. AAG could exist in multiple isoforms within different individuals. Around 42% of the molecular weight of AAG is heterogenous carbohydrate composition, which constitutes 5 asparagine linked branched glycan chains which contains approximately 11% sialic acid. N-linked gycans resulting extensive gycosyalation gives protein a negative charge at neutral ph and also increases its water solubility,The protein structure contains. 21% α-helix and 21% β-sheet. The carbohydrate group of AAG does not affect conformation of the protein component. The physiological function …show more content…
GLOBULINS There are various plasma globulins which have been identified in the blood plasma
1) Α1 globulin: also known as transcortin. It binds to a number of steroidal drugs such as cortisone and prednisone so also known a corticosteroid binding globulin
2) A2 globulin: also known as ceruloplasmin. It generally binds to vitamins A, D, E and K and also to cupric ions.
3) Β1 globulin: also known as transferrin and it binds to ferrous ions.
4) B2 globulin: it binds to carotinoids.
5) Y-globulin: It generally binds to antigens.
METHODS FOR MEASUREMENT OF PPB
Many successful methods to measure the degree of plasma protein binding of drugs have been derived. All these method work by physically separating the unbound drug from the bound drug and calculating the relative fractions.
Some beneficial techniques to measure plasma protein binding are:
a) Equilibrium dialysis
b) Ultrafiltration
c) Ultracentrifugation
d) Microdialysis
e) Gel filtration
f) Circular dichroism
g) Microspheres of albumin
There are some other techniques also which are utilized to a lesser extent such as micro-extraction and optical biosensors such that they could be used for highly protein bound drugs. None of the methods could be judged as superior over others as all these methods possess some advantages as well as disadvantages.
A) EQUILIBRIUM DIALYSIS:
It is a well accepted and a popular metod used in PPB measurement. This
Thiol groups are important to protein folding and forming disulphide bonds that are essential to protein structure. Determining the number of thiol groups in a protein is important in determining the tertiary structure of the protein. The ovalbumin is the experiment was purified from egg white using centrifugation and ammonium sulphate precipitation and then the thiol groups identified using DTNB and spectroscopy. The ovalbumin was found to have one thiol group; from this we were also to infer that DNTB alkylates thiolgroups; whereas SDS keeps proteins denatured.
Glucocortiocoids= Glucocorticoids (GC) are a class of steroid hormones that bind to the glucocorticoid receptor, which is present in almost every vertebrate animal cell. GCs are part of the feedback mechanism in the immune system that turns immune activity (inflammation) down. They are therefore used in medicine to treat diseases that are caused by an overactive immune system, such as allergies, asthma, autoimmune diseases and sepsis. GCs have
Absorption – “How the drugs enter the circulation process through the body, and how they resist general breakdown by the stomach, liver, and the intestines”. Some of the factors that affect the absorption of drugs in the body is as follows, “acidity of the stomach, Physiochemical properties, Presence of food in the stomach or intestine, and Routes of administration”,
The specificity of albumin binding experiment was to determine the binding interactions that occur between serum albumin and three synthetic dyes with the use of electrophoretic procedure. Whole blood, or plasma. Clots upon standing and if the clot is removed, the remaining straw colored fluid is called serum. The major protein in serum is albumin which functions as a carrier molecule for the transport of certain small molecular weight compounds in blood. Molecules that bind to serum albumin are fatty acids, hormones and some synthetic dyes. In this experiment the synthetic dyes used are Bromophenol Blue, Ponceau S and Orange G. we observed that free dyes not bound to albumin migrate faster that albumin or dyes bound to albumin. This
Second, in order to further confirm the information about characteristics and function of the targeting protein that we have
Gelatin is observed to have a lower absorbance reading than lysozyme in only the Bradford assay, while in the BCA assay gelatin was observed to have about the same absorbance as lysozyme. In Bradford assay, the color yield for proteins with higher content of tryptophan, tyrosine, or cysteine residue, will be higher. The observed protein sensitivities did not correlates with the amino acid content in the Bradford assay. As presented in Table I, the mole fractions of lysine and arginine in BSA were 10 mole percent and 4 mole percent, respectively. The sensitivity should have been higher in BSA than in the Bradford assy. However, the observed sensitivities did correlates with the amino acid contents in the BCA assay.
breakdown of drugd within the body and the characteristic interactions of a drug in terms of its
Steroids are a group of liquids with a complex molecule containing carbon atoms in four interlocking rings that form a hydrogenated cyclopentophenanthren-ring system the rings contain six atoms and the fourth contains five.steroids can be important in the body and include hormones such as gonadal,sex steroids and corticosteroids. One group of steroids are produced mainly by adrenal cortex. They fall into three groups glucocorticoids,mineralocorticoids and sex hormones. Glucocorticoids have antiinflammatory properties reducing vasodilatation stabilizing cells and decreases the release of histamine it maintains the normal permeability of blood which prevents oedema. It also inhibits production of prostaglandins that mediates the effects of inflammation. They are used
For the second part of the experiment, one had to use the knowledge learn from viewing protein molecules in FirstGlance in Jmol to analyze the protein PDB ID: 4EEY. The analysis of this protein was done using the RSCB protein data bank (PDB) at (http://www.rcsb.org/pdb/home/home.do).2
The recoveries of voriconazole, voriconazole N-oxide and internal standard were determined by comparing the peak areas of equivalent concentrations spiked in blank plasma before and after protein precipitation. Analytes with equivalent concentrations were prepared in precipitated blank plasma or in methanol which were used as references, and peak area of anaytes were measured to calculate the matrix effect. All experiments were performed at three concentration levels of QC in five
Corticosteroids are a part of the steroid hormones family, which include glucocorticoids that are synthesized and secreted by the adrenal cortex (Simon, et al., 2013, p. 545). On the flipside anabolic steroids are controversial drugs that are synthetic variants of testosterone (Simon et al., 2013, p. 45).
ATCH take control to allow the middle and inner parts of adrenal cortex to release glucocorticoids. This hormone helps to promote the breakdown of muscle proteins to amino acids, which are taken up by the liver from the bloodstream. The liver will break down these excess amino acids to glucose, which enter the blood. Furthermore, glucocorticoids are also promoted the metabolism of fatty acids rather than carbohydrates. The glucocorticoids also counteract the inflammatory response that leads to pain and swelling of joints in arthritis and bursitis. The administration of cortisone aids these conditions because it reduces inflammation. Very high levels of glucocorticoids in the blood to suppress the body’s defense system, including the inflammatory response that occurs at infection sites. Cortisone and other glucocorticoids can relieve swelling and pain from inflammation, but by suppressing pain and immunity,
"Absorption depends on the drug’s ability to cross cell membranes and resist extensive breakdown by the stomach, liver, and intestines.
Hence, the experimental procedure was executed as detailed here. A syringe fitted with a hypodermic needle was used to infuse the drug into the organ bath away from the tissue sample. To help maintain fair testing conditions it was done such that throughout the experiment the drug was injected at the same speed at the same location. Prior to injecting, the syringe was checked for bubbles of air accidentally acquired during uptake of the drug, as this would cause alterations in volume of drug and thus alterations in FBC. Time at which the drug was added was recorded using the Biopac software. Subsequently, two minutes was allowed for the interactions and binding of the drug to occur, in which time the live recordings were monitored for changes. Once sufficient time was allowed to see a significant change in
The accuracy parameter conducted by using the standard addition method. The proposed method afforded a recovery of 99.49-101.54% after the additional standard drug solution was spiked with the analyzed test solutions. The recovery percentages for Lamivudine, Zidovudine and Nevirapine were in the ranges from 99.80 to 101.06%, from