Oprelvekin

It is a Hemtopoeitic Growth Factor. It is interleukin-11(IL-11). It is a nonglycosylated protein involved in the increase of platelet count.

Filgrastim

It is an endogenous glycoprotein controlling the production of neutrophils in the bone marrow.

Darbepoetin

It is a Hematopoietic growth factor. Darbepoetin is a longer acting type of erythropoietin which differs from erythropoietin in respect of two additional carbohydrate chains. And because of these two additional chains, its biological activity is increased.

Pharmacokinetics:
Darbepoetin has less value of clearance and have a half life of about three times than that of erythropoietin. It has late start of action and that is why it cannot be used for acute anemia therapy.

Administration:
Sometimes iron is given along with darbepoetin for a better response. Usually subcutaneous route is superior but in the patients undergoing dialysis of kidney it is given intravenously.

Adverse effects:
It may cause hypertension and arthralgia.

Erythropoietin

It is Hematopoeitic Growth Factor. It is a glycoprotein. It is usually made in the kidney.

Recombinant DNA technology is done to obtain human erythropoietin.

Mechanism of action:
It activates the multiplication (proliferation) and development of specialized functions (differentiation) of red blood cells by its interaction with particular erythropoietin receptors on the originators of red cells in the bone marrow.

Therapeutic uses:
It is used for the treatment of patients with end stage renal failure, significant anemic conditions caused by human immunodeficiency virus and anemia in patients of cancer.

Adverse effects:
It may cause hypertension and allergic conditions. Thrombotic complications may also develop. Minimum effective dose must not exceed 12g/dL of hemoglobin concentration. As more than 12g/dL of concentration can cause considerable life threatening effects on the heart and finally can lead to death.

Folic Acid

It is also called as folacin, folate or pteroylglutamic acid. It is a member of vitamin-B complex family and is essential in the making and maturation of red blood cells. It is present in liver, green vegetables, fruit and yeast, in peptide linkages.

Daily requirements:
Daily folic acid requirement is about 50 µg in normal adults.

Mechanism of action:
Folic acid is a preceding compound for many of the folate cofactors which are important for the synthesis of DNA by the transfer of a carbon atom such as
1. Formation of purine
2. Formation of thymidylic acid from deoxyuridylate

Pharmacokinetics:
Absorption:
Dietary folate in the form of polyglutamate is converted into monoglutamate 5-CH3-H4 folate and it is well absorbed in the proximal jejunum.

Distribution:

It is distributed widely in the body with the help of blood stream. Usually, 5-20 mg of folic acid is preserved in the liver.

Elimination:
More amount of the folic acid, if ingested, is excreted via urine and feces.

Folic acid deficiency:

Its deficiency can be caused by:
1. Greater demand for folic acid such as that in pregnancy or lactation
2. Poor absorption due to any pathological cause of the small intestine
3. Intake of alcohol
4. Dihydrofolate reductase inhibitors such as methotrexate or trimethoprim can also cause its deficiency

Therapeutic uses:
It is used to treat
1. Folic acid deficiency and
2. Megaloblastic anemia which is primarily caused by the decreased production of purines and pyrimidines leading to decreased ability of erythropoietic tissue for the formation of DNA.

Dosage:
It is given in the dose of 1 mg orally per day.

Adverse effects:
It causes no adverse effects as it is immediately excreted through urine.

Sphingolipids

They belong to a class of lipids i.e. Membrane lipids. Sphingolipids come from the combination of sphingosine (a long chain base), which is an amino alcohol (and aliphatic in nature), and fatty acid.It is the simplest sphingolipid and is also referred to as sphingoid base. They have a head, which is polar in nature, and two tails, which are nonpolar.

The following mnemonic will help you a lot in remembering the structure of shingosine.



Sphingolipids are present in plasma membranes.

Types of sphingolipids:

1. Ceramide:
It consists of Fatty acid chain and sphingosine linked through amide linkage. It is ordinarily present in all sphingolipids.

These are the precursors of glycolipids and phospholipids having a wide range of function in the tissues.

2. Sphingophosphlipids
     a. Sphingomyelin
     It consists of Phosphoethanolamine or phosphocholine and 1-hydroxy group of a ceramide linked through ester linkage.Sphingomyelin is structurally similar to phosphatidylcholine but biologically and physically it is different.

3. Glycosphingolipids:

    a. Cerebrosides
    b. Sulfatides (Sulfated cerebrosides)
    c. Globosides
    d. Gangliosides

Fatty acids in Sphingolipids:
Fatty acids of sphingolipids are completely different from those of glycerolipids. They have very long chains and the number of carbon atoms may range from 25 to 35 in number.
Polyunstaurated fatty acids are rarely present in sphingolipids but sphingomyelins of testes and spermatozoa have this acid.
Monoenoic fatty acids and very long chain fatty acids are producd by specific elongases.
Free long chain fatty acids are converted in to free 2-hydroxy acids in vitro as a result of fatty acid 2-hydroxylase.It is an integral membrane protein of endoplasmic reticulum.

Synthesis of sphingolipids:

Synthesis of sphingolipids takes place in Endoplasmic reticulum. Following is the pathway for the synthesis of sphingolipids.

In the first step, Palmitoyl-CoA alongwith serine results into beta ketosphinganine to sphinganine to N-acylsphinganine to Ceramide containing sphingosine to Cerebroside and sphingomyelin.

Sphingomyelin cycle:
Sphingomyelin cycle is used to show a relationship between the metabolic products of sphingolipids.

Free sphingosine and certain other long chain bases work as mediators for many of the cellular processes. Sphingosine 1-phosphate and ceramide 1-phosphate increases mitosis.

Degradation of sphingolipids:
These are degraded by lysosomal enzymes.

Presence of sphingolipids in Micro-organisms:
Sphingolipids are also found in some genera of bacteria like sphingomonas and sphingobacterium.

Uses of sphingolipids:
They work as the site of adhesion of extracellular proteins. Sphingolipids are important in cell recognition and signal transmission/transduction.

Sphingolipids form the myelin sheath around the nerves in central nervous system.

Diseases in which sphingolipids are involved:

1. Microbial infections
2. Diabetes
3. Alzheimer's disease
4. Certain cancers
5. Some diseases of the respiratory and cardiovascular systems and
6. Some of the neurological syndromes

References:
Murray S. Webb, Marcel B. Bally, Lawrence D. Mayer, James J. Miller, Paul G. Tardi, Sphingosomes for enhanced drug delivery. Patent number: 5814335.

Further Reading:
Delivery System Handbook for Personal Care and Cosmetic Products : Technology, Applications and Formulations (Breakthroughs in Personal Care and Cosmetic Technology) by Meyer R. Rosen

Encyclopedia of Pharmaceutical Technology by James Swarbrick

Hannun, Y. A. 1994. The sphingomyelin cycle and the second messenger function of ceramide. Journal of Biological Chemistry, Vol. 269, No. 5.

http://lipidlibrary.aocs.org/lipids/introsph/index.htm

Copyright (c), 2008, jeepakistan.blogspot.com

Skeletal system pro

Skeletal system pro

This software is an elearning tools and can be used as a reference for skeletal and ligament studies. This software is helpful in learning a topic in anatomy.

Tags:
iPhone apps, Medical

Further Reading:
http://www.3d4medical.com/Skeletal-System-application_APP1.html