Wednesday, June 18, 2008

Migraine and Triptans

Migraine and Triptans


Most of us have occasional headaches that are relieved by over-the-counter medications. When headaches are frequent or unrelieved by OTCs we usually consult a physician or tend to increase the doses of medications or even try home remedies… But at times, in some people/patients this does not bring and relief. The answer to this may be MIGRAINE. Unfortunately about of all the patients with migraine are not properly diagnosed and those who are, don’t receive proper treatment. .

Migraine has been first described in the EBERS PAPYRUS (of about 1550 BC is among the most important medical papyri of ancient Egypt. It is one the two oldest preserved medical documents anywhere). In 400 B.C Hippocrates used the method of “vomiting“ to treat migraines. It was Galen in 200 A.D who first introduced the term migraine from the Greek word hemicraine (meaning “half of the head”).

Migraine is caused by the vasodilatation of frontal branch of the superficial temporal-artery leading to neurogenic inflammation, due to release of chemicals like Neurokinin-(mediators of inflammation) from the primary sensory nerve fibres involved in pain transmission. Due to dilatation the nerve fiber coiling the artery gets stretched which gets depolarized and activated causing pain sensation.

Fig:Increased blood flow in an area of mesencephalon (arrow)

Various other theories claim to explain the pathophysiology of migraine
a. Depolarization theory
b. Vascular Theory
c. Serotonin Theory
d. Neural Theory
e. Unifying Theory (Combination of Vascular and Neural theories)

Early symptom, where development of the condition is prominent. Symptoms such as headache, fever etc. are seen during this phase.
2. Aura - A kind of disturbance seen in migraine sufferers before the migraine headache.
3. Pain - Headache phase where the actual migraine headache is seen. High levels of headache is prominent here.
4. Postdrome - The final phase of migraine headache.

Migraine may be diagnosed by symptoms and family history. Sometimes an MRI or CT scan is obtained to rule out other causes of headache like sinus inflammation or a brain mass. In the case of a complicated migraine, an EEG may be needed to exclude seizures. Rarely, a lumbar puncture (spinal tap) might be performed.

a.Bright lights, loud noises, and certain odors or perfume
b. Change in sleep patterns
c. High Stress
d. Smoking & alcohol
e. Allergic reactions
f. Menstrual cycle fluctuations & birth control pills
g. Foods containing tyramine.

Migraine with aura: Migraine precedes with visual disturbances before the headache starts.
Migraine without aura: Does not have the aura stage

Aura consisting of at least one of the following:
Fully reversible visual symptoms
Fully reversible sensory symptoms
Fully reversible dysphasia.

TREATMENT .... to be continued

23:40 18th may


Simplified molecular input line entry specification [SMILES]

SMILES is used for specification for describing molecules.

SMILES:: The simplified molecular input line entry specification or SMILES is a specification for unambiguously describing the structure of chemical molecules using short ASCII strings.


ASCII (American Standard Code for Information Interchange, generally pronounced ass-key) is a character set and a character encoding based on the Roman alphabet as used in modern English. It is most commonly used by computers and other communication equipment to represent text and by control devices that work with text.
ASCII specifies a correspondence between digital bit patterns and the symbols/glyphs of a written language & is used on nearly all common computers, especially personal computers and workstations.
ASCII is, strictly, a seven-bit code, meaning that it uses the bit patterns representable with seven binary digits (a range of 0 to 127 decimal) to represent character information.ASCII is one of the most successful software standards ever.


SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three- dimensional models of the molecules.

The original SMILES specification was developed by Arthur Weininger and David Weininger in the late 1980s. It has since been modified and extended by others. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI.

The IUPAC International Chemical Identifier (InChI), developed by IUPAC and NIST, is a digital equivalent of the IUPAC name for any particular covalent compound. Chemical structures are expressed in terms of five layers of information — connectivity, tautomeric, isotopic, stereochemical, and electronic.

TYPES OF SMILES:: Canonical SMILES and Isomeric SMILES

The term Canonical SMILES refers to the version of the SMILES specification that includes rules for ensuring that each distinct chemical molecule has a single unique SMILES representation. A common application of Canonical SMILES is for indexing and ensuring uniqueness of molecules in a database.
The term Isomeric SMILES refers to the version of the SMILES specification that includes extensions to support the specification of isotopes, chirality, and configuration about double bonds. A notable feature of these rules is that they allow rigorous partial specification of chirality.

Graph-based definition of SMILE

In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph.
depth-first and tree-traversal are two types of algorithms”
The chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree.


Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as [Au] for gold. The hydroxide anion is [OH-]. Brackets can be omitted for the "organic subset" of B, C, N, O, P, S, F, Cl, Br, and I. All other elements must be enclosed in brackets. If the brackets are omitted, the proper number of implicit hydrogen atoms is assumed;

· For instance the SMILES for water is simply O and that for ethanol is CCO. (i.e Hydrogens are trimmed off)

· The double-bonded carbon dioxide is represented as O=C=O and the triple-bonded hydrogen cyanide as C#N.

Branches are described with parentheses, as in Propionic anc and Floufororm

· CCC(=O)O for propionic acid

· C(F)(F)F for fluoroform, which could also be described by the non-canonical formula FC(F)F.

· Cyclohexane is represented as C1CCCCC1, the idea being that the two 'number ones' label the same position in the molecule, thus forming a ring with six carbons. It is to be noted that the label is the numeral (in this case the 1) rather than the combination of 'C1'.

· Aromatic C, O, S and N atoms are shown in their lower case 'c', 'o', 's' and 'n' respectively. Bonds in an aromatic cycle are rarely marked explicitly except in SMARTS search patterns. Thus Benzene is c1ccccc1.


SMARTS is a modification of SMILES that allows, in addition to the SMILES elements, the specification of wildcard (*) atoms and bonds. This is used in specifying search structures and is widely used in chemical database search applications. This practice has led to a common misconception that chemical substructure search is achieved computationally by matching SMILES/SMARTS strings, when, in fact, it is achieved by the computationally more intensive search for subgraph isomorphism in the graphs reconstructed from the SMILES representations.




any pair of attached aromatic carbons


aromatic carbons joined by an aromatic bond


aromatic carbons joined by a single bond (e.g. biphenyl).


any aliphatic oxygen


simple hydroxy oxygen


1-connected (hydroxy or hydroxide) oxygen


2-connected (etheric) oxygen


the 1st four halogens.


must be aliphatic nitrogen AND in a ring


any arom carbon OR H-pyrrole nitrogen


(arom carbon OR arom nitrogen) and exactly one H


two atoms connected by a non-ringbond


two atoms connected by a non-aromatic ringbond


two carbons connected by a double or triple bond


aliphatic carbon with two hydrogens (methylene carbon)


( NOT aliphatic carbon ) AND in ring


must be aliphatic nitrogen AND in a ring


H-pyrrole nitrogen


any arom carbon OR H-pyrrole nitrogen


All SMILES expressions are also valid SMARTS expressions, but the semantics changes because SMILES describes molecules whereas SMARTS describes patterns. The molecule represented by a SMILES string is usually, but not always, matched by the same string when used as a SMARTS.

Other 'linear' notations include the

1. Wiswesser Line Notation (WLN), ROSDAL and SLN (Tripos Inc.)

2. SYBYL Line Notation specification for unambiguously describing the structure of chemical molecules using short ASCII strings.

3. Recently, the IUPAC has introduced the InChI as a standard for formula representation.


21:30 18th may

Wednesday, June 4, 2008

Stress Headaches

ave you been to your doctor lately complaining about that unexplained bout of headaches or body pain? Only to be told that there's nothing wrong. Well, it could be work-related stress that is causing aches, depression and other health problems say health experts.

A survey conducted by India's industry body Assocham has revealed that "the menace of stress and mental fatigue has intensified in recent times at the top and middle positions of sectors comprising construction, shipping, banks, government hospitals, trading houses, electronic and print media, courier companies, small-scale industries, retail and card franchise companies".

As more of the Indian workforce rushes to catch up with the deadlines, the boundary between home and work is becoming blurred. As the work hours stretch and more and more jobs entail odd work hours, the stress levels among the Indian workers is increasing in an alarming way causing many health problems……

Well stress leads to a certain type of headache known as “Tension Headaches”
What are tension headaches??

What's in a name?

"Tension headaches" was first used to suggest that these headaches were the result of psychological stress and tension. Since they are not psychological in nature, that's misleading. "Muscle contraction" was used because increased activity of the pericranial muscles (pertaining to the periosteum of the skull, the periosteum being the fibrous membrane that lines the skull.) is so often involved. When researchers realized that was true just as often in episodes of migraine disorder, the use of "muscle contraction headache" was pretty much abandoned, and the term "tension-type headache" came into use.

"Tension-type" headaches, or tension headaches, are the most common type of headache. About 30% to 80% of adults occasionally experience this kind of headache. Tension headaches are more common among women than men. These headaches are sometimes called stress headaches, muscle contraction headaches, daily headaches, or chronic non-progressive headaches.

Tension headaches usually begin gradually and often occur in the middle of the day. A tension headache may occur on an episodic basis (less than 15 days per month) or on a chronic basis (daily or more than 15 days per month). Most people with episodic tension headaches have them no more than once or twice a month, but the headaches can occur more frequently.

What Causes Tension Headaches?

There is no single cause for tension headaches. This type of headache is not an inherited trait that runs in families. In some people, tension headaches are caused by tightened muscles in the back of the neck and scalp. In others, tightened muscles are not part of tension headaches, and the cause is unknown.

Tension headaches are usually triggered by some type of environmental or internal stress. The most common sources of stress include family, social relationships, friends, work and school.

Episodic tension headaches are usually triggered by an isolated stressful situation or a build-up of stress. Daily stress can lead to chronic tension headaches.

What Are the Symptoms?

In mild to moderate tension headaches, there is a constant, band-like pain or pressure that lasts from 30 minutes to all day. Tension headaches tend to be moderate or mild and are rarely severe. Unlike migraines they are not usually unilateral, throbbing or associated with light and sound sensitivity or nausea and vomiting. Other features of tension headaches may include:

  • Headache upon awakening
  • General muscle aches
  • Difficulty falling asleep and staying asleep
  • Chronic fatigue
  • Irritability
  • Disturbed concentration
  • Mild sensitivity to light or noise
  • Occasional dizziness

Chemical changes

Researchers now believe that tension headache may result from changes among certain brain chemicals — serotonin, endorphins and numerous other chemicals — that help nerves communicate. These are similar to biochemical changes associated with migraine. Although it's not clear why the chemical levels fluctuate, the process is thought to activate pain pathways to the brain and to interfere with the brain's ability to suppress the pain. On one hand, tight muscles in the neck and scalp may contribute to a headache in someone with altered chemical levels. On the other hand, the tight muscles may be a result of these chemical changes.

Another chemical in the body that may play a role in tension headache is nitric oxide, which is involved in the transmission of nerve impulses. Overproduction of nitric oxide has been linked to chronic tension headache and migraine. And substances that block the production of nitric oxide have been shown to reduce the muscle tightness associated with tension headache.

Because both tension headache and migraine involve similar changes in brain chemicals, some researchers believe that the two types of headache are related. A majority of people diagnosed as having migraine also get an occasional tension headache, and a quarter of people diagnosed with tension headache get occasional migraine. Some experts speculate that migraine may develop from the regular occurrence of tension headache. The distinctive migraine features form as the pain becomes more severe. Other research suggests that mild migraine is in reality a type of tension headache.

How Are Tension Headaches Treated?

Treatment for this type of headache usually includes nonprescription pain relievers such as aspirin or ibuprofen. Prescription medications (antidepressants like Diazepam) may be needed in some cases.

Therapies such as stress management or biofeedback may be used in an effort to reduce or prevent tension headaches.

14:30, 4th June