Brain is most important part of your body, needed to think and perform your work perfectly; a headache sometimes paralyzes you completely and jams the daily routine. Recognizing your child’s headache and treating it, takes special attention and effort. You may not be always able to diagnose immediately his headache as kids of different age group can have different reasons of headache.

Treating Your Child’s Headache

Whenever your child have headache first and foremost thing which needs to be done is to get to the actual cause of the headache and jot up right remedy for it. There are large numbers of causes of a child’s headache, and each one has a distinctly different remedy. For example, if your child hits his or her head on something resulting in a headache, you may need to rush to a doctor, in order to ensure that the headache is not due to internal injuries.

Poor eyesight can also be major causes of child’s headaches. Parents don’t realize it until the child vision gets really bad and he or she complains that the vision is blurred. Your child’s headache can also be caused by stress or another existing medical condition for which drugs are being administered. Finding the real cause of headache can really help to find the right remedy without having any side effects.

Headache Medication for Children

A headache medication can be accessed without a prescription too if you really know the cause and right kind of medicine to take. You must pay attention to the indication written on the back of the medicine pack and never overdose your child to eradicate child’s headache as soon as possible. If the headache persists even after taking the maximum dose prescribed on the drug bottle, you should consult a doctor.

Natural remedies such as homeopathic drugs and herbs can be other ways of treating a child’s headache. Natural remedies like Acupuncture can also work miracles when done regularly. These natural remedies for headaches are not only available for all ages, but they are also becoming more popular everyday because they have no side effects and sometimes it work quicker than the traditional medications.

Helpful Tips

Educate yourself about your child’s present health state; in order to know precisely why he or she is suffering from headaches and what would be the best remedy for them. Remember that even child’s headache medications can have side effects such as, diarrhea and nausea. Therefore it should be administered with plenty of fluids and eatables.

If you are interested to know more about child’s headache then please visit to Child Headache



Butalbital Blog

Who get migraine?

Physiologically, migraine headache is a neurological condition that is more commonly known to afflict women than men. Women experience migraines at least three times more often than men, probably because of hormonal changes. However, migraines can occur in children also, but they mostly appear in people in their twenties or thirties.

Studies have revealed that migraines could be inherited. For example, if one parent is afflicted with migraine, there is a 40% chance that the child will have migraine. If both parents have migraine, the probability increases to 75%.

Although, there is no specific migraine personality, most migraine sufferers have been found to be perfectionists, high-strung, conscientious, orderly, analytical and critical.

Symptoms and treatment of migraine

Symptoms of Migraine

Migraine pain generally differs from other types of headache; it has specific symptoms that may vary in intensity, character, frequency and duration. Migraine attacks can appear from a couple of times a year to almost every day. The two main types of migraine are:

Classical Migraine – migraine with aura Common Migraine – migraine without no warning or aura

A few migraine patients may experience an aura, which is normally treated as a sign of the pain to come. The aura consists of bright spots or zigzag lines and blurred vision or temporary visual loss. In rare cases numbness or tingling of the face and lips can also be observed. However, these symptoms generally disappear within an hour and are then replaced by a headache. In some cases the aura may not be followed by headaches.

Common migraine headache mostly begin without warning and are most commonly experienced by children. Common symptoms of this migraine are associated with:

Intense head pain (the pain begins on one side of the head and spreads downward to the eye, face and even neck; the pain can also switch sides or affect both sides at once) Relentless throbbing or pounding deep in the head Nausea Vomiting Strong and painful reactions to light and loud noises Activity associated pain (the simple act of moving may be difficult during the migraine attack) Not being able to carry out day to day activities. The need to lie down during attacks

People may sometimes experience all or some of the symptoms which are either moderate or severe. Migraine attacks may last from anywhere up to four hours to three days. This affliction has the potential to severely disrupt your work and family life as well as your social activities.

Migraine trigger

Migraine, it is believed, is triggered by changes in the neurotransmitters and blood vessels in the brain. However, certain factors have been identified that can trigger attacks in susceptible people. They are:

Stress (or sometimes the relief of stress) Lack of food or infrequent meals Certain foods products containing monosodium glutamate, caffeine, tyramine or alcohol Overtiredness (both physical and mental) Changing sleep patterns (e.g. weekend lie ins, sleeplessness or shift work) Hormonal factors (e.g. monthly periods, contraceptive pill, HRT or menopause) Extreme emotions (e.g. anger, grief etc.) Physical activity Environmental factors (e.g. loud noise, bright or flickering lights, strong perfumes, hot stuffy atmosphere, VDUs etc.) Climatic conditions (e.g. strong winds, extreme heat or cold)

For most people, afflicted with migraines, it is usually not any one trigger but a combination of factors which collectively work against a person’s threshold and an attack is triggered.

Cefaly medical device for migraine

Cefaly is a medical device that relieves pain in people suffering from migraines and cluster/tension headaches as well as trigeminal neuralgia and frontal sinusitis. It has a full EEC medical certification. A patented system, it bears the ISO and CE medical mark.

The unit consists of a band that is worn around the front of the head and it then sends electrical impulses through an electrode patch placed in between the eyebrows. This device works on the trigeminal nerves at the front of the face. It works at three programme levels. They are:

Programme 1 – Is a treatment programme, based on TENS technology. It works on blocking the flow of pain at the entrance of the spinal cord. Programme 2 – Is the preventive or endorphinic programme. It increases the endorphins (natural painkillers) in the central nervous system. Programme 3 – Is the anti-stress and relaxation programme.

Numerous tests and clinical studies have been conducted that prove that Cefaly is effective, with almost 85% of its users being extremely satisfied with the results.



migraine

Percocet, Tylox & Percodans are the different trade names of Oxycodone products.

Oxycodone is a 14-hydroxydihydrocodeinone, semi-synthetic opioid analgesic that occurs as a white, odorless, crystalline powder having a saline, bitter taste. It is a potentially addictive opioid analgesic medication synthesized from thebaine.

Oxycodone Prescription:

It was first introduced to the US market in May 1939 and is the active ingredient in a number of pain medications commonly prescribed for the relief of moderate to heavy pain. Oxycodone is prescribed for moderate to high pain relief associated with injuries, bursitis, dislocation, fractures, neuralgia, arthritis, and lower back pain. It is also used postoperatively and for pain relief after childbirth. It is a commonly used medication for treatment of pain in cancer patients.

Oxycodone Abuse:

Oxycodone has a high abuse potential as it is a central nervous system (CNS) depressant. In the United States, oxycodone is a controlled substance both as a single agent and in combination with products containing acetaminophen (Percocet, Tylox), ibuprofen or aspirin (Percodan). Oxycodone’s action appears to work through stimulating the opioid receptors found in the central nervous system that activate responses ranging from analgesia to respiratory depression to euphoria.

Oxycodone abusers ingest the drug in a variety of ways. They often chew the tablets or crush the tablets and snort the powder. As oxycodone is water soluble, crushed tablets can be dissolved in water and the solution injected.

Effects of Oxycodone Abuse:

Side effects of Oxycodone include constipation, dryness of the mouth, confusion, sedation, light-headedness, respiratory depression, nausea, vomiting, headache, & sweating etc while symptoms of overdose include slow breathing, seizures, dizziness, weakness, loss of consciousness, coma, confusion, cold or clammy skin & small pupils to name a few.

People who take the drug repeatedly can develop a tolerance or resistance to the drug’s effects. Thus, a cancer patient can take a dose of oxycodone on a regular basis that would be fatal in a person never exposed to oxycodone or another opioid. Most individuals who abuse oxycodone seek to gain the euphoric effects, mitigate pain, and avoid withdrawal symptoms associated with oxycodone or heroin abstinence.

Percocet, a narcotic analgesic, is used to treat moderate to moderately severe pain. It consists of two drugs—acetaminophen & oxycodone. Acetaminophen is used to reduce both pain and fever. Oxycodone, a narcotic analgesic, is used for its calming effect and for pain. Serious adverse reactions that may be associated with Percocet tablet use include respiratory depression, apnea, respiratory arrest, circulatory depression, and hypertension

Percodan is a potent compound painkiller used to treat moderately severe to severe acute pain. Percodan consists of aspirin & oxycodone, a potent opioid agonist. At one time one of the most widely prescribed painkillers, Percodan has largely been replaced by alternative oxycodone compounds containing acetaminophen (Tylenol) instead of aspirin, such as Percocet.

Federal Regulations:

Like other opioid medications, Tylox, Percodan, Percocet tablets are subject to the Federal Controlled Substances Act. After chronic use, Tylox, Percodan, Percocet tablets should not be discontinued abruptly when it is thought that the patient has become physically dependent on oxycodone.

Oxycodone Testing:

Urine testing for oxycodone may be performed to determine its illicit use and for medical reasons such as evaluation of patients with altered states of consciousness or monitoring efficacy of drug rehabilitation efforts. Based on pharmacokinetic data, the approximate detection duration for a single dose of oxycodone is roughly estimated to be one to two days following drug exposure.

Oxycodone, like other opioids, has been diverted for non- medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.



Fioricet

You can really eliminate pain with hypnosis. The saying “no pain, no gain” is really not true. Do you remember all of the times pain has hindered you from taking part in activities that you enjoy? Partaking in sports and even sitting can be unbearable when you are in pain.

However, to say that “pain is all in your head” can really be true. If that is the case then the cure should be all in your head too! With help of self-hypnosis, pain can completely disappear. Despite what most people think, hypnosis is simply a mental state where messages can connect with the unconscious easier. The state of hypnosis is characterized by very deep relaxation. With regular practice of a hypnosis pain elimination regimen, you will feel more peaceful over all.

Pain signals that something in your body is amiss so pain is technically a good thing. Make sure a doctor check you out to ensure that the pain is not indicating a harmful condition. Then it’s time to manage and even eliminate the pain.

There is really no danger in a self-hypnosis pain relief program. It is not true that you can “get stuck” in a hypnotic state. The worst that might happen when you use hypnosis for upper pain reduction is that you could fall into a natural state of sleep for half an hour. Compare to all of the nights that discomfort has prevented you from sleep!

One can’t say that a hypnosis pain management system is the same as sleep though. That is probably the biggest misconception about hypnosis. When you are asleep, you are unconscious, and if you are unconscious you cannot hear anything. If you can’t hear anything, the hypnotist cannot help you. On the contrary, hypnosis is actually a state of keen awareness.

Being consciously aware of everything, a hypnosis pain management program can help both physical and mental causes and lead to many successful avenues to do away with pain. As you know, medications merely block the reception of the physical symptoms of pain on a temporary basis. Hypnosis pain regimens can in fact lessen the amount and strength of pain signals that you perceive. You can actually reprogram your body to send less pain-inducing chemicals to your receptors. This means that you can use fewer pain killing drugs, often no medications at all.

You have probably heard of endorphins, the opiate-like chemicals that are generated in our brains. Endorphins are the chemicals that cause people who train to get a high when they workout hard. Using hypnosis, you can also learn how to program your brain to create pain-relieving endorphins on demand! And send them to the painful part of your body where they are required.

With help of endorphins, the brain is capable of inducing analgesia, which is a mild anesthesia, as well as full anesthesia (numbness). Medical journals are full of accounts both in modern times, as well as in pre-anesthesia days, when invasive surgery has been done under hypnoanesthesia.

Hypnosis can also work to program the mind to direct your attention away from pain. In this way you will perceive far less discomfort. Also, hypnosis pain management programs can help our mind realize and understand that the pain is there, but not to let us suffer from it. A certified hypnotherapist will be familiar with how to fully address additional hypnotic suggestions that will aid in your recovery.

A really effective hypnosis pain remedy lies in neuro linguistic programming, NLP. No doubt that after living with chronic pain or left side pain, you may be cynical that a hypnosis pain program will help. In many cases, NLP methods really work far better for modern thinkers than traditional hypnosis does. It was actually developed for people like you who are brought up to analyze and question everything. Analyzing can mean that we tend to put up barriers to the acceptance of hypnotic suggestions.



Butalbital

“A migraine is like a tornado; it attacks fast without any warning and wreaks havoc.”

Migraines usually start during the teenage years or early in adult life, affecting more women than men with a ratio of three to one. Migraines are caused from constricted (tightening) arteries that supply blood flow to the brain. When the arteries constrict, blood flow to the brain is reduced as well as the brains oxygen supply. The brain reacts by dilating (enlarging) arteries to meet the brain’s need for energy. The dilation spreads to the arteries in the neck and scalp and is the culprit of the pain in migraines.

If you live with migraines, make sure to have your Doctor rule out an underlying illness or other medical conditions that mimic migraines with the appropriate tests: for example, x-rays determining sinus infection, EEG for seizure activity or a CAT scan to detect blood clots or a brain tumor. Your Dr. may determine a drug to help ease your pain.

Eight Migraine Triggers

1. Cerviogentic Headache:

Some people who have a tender neck and suffer from sore bone and joint problems are diagnosed with this type

2. Temporomandibular Migraine:

Triggered by teeth grinding

3. Sinus Migraine:

Triggered by allergies and caused by excessive mucous and often accompanied by a fever. If you have this type of migraine, you may experience pain around both eyes and also may feel nauseated and sensitive to light.

4. Genetic Migraines:

Studies have lined a gene to people affected with migraines. Often when the gene for migraines is passed on to the next generation, the recipient will also experience headaches around the same age as the person who passed on the migraine.

5. Stress Migraine:

Stress can be a major contributing factor to the onset of a migraine. Type A personalities are more likely to experience migraines. Type A is ambitious, bright, perfectionist, emotionally repressed, cautious and has a decreased ability to manage stress. However, this is the easiest type of migraine to treat because a type A personality can acquire the skills necessary to manage stress.

6. Hormonal Migraine:

Fluctuating hormones in women are often the cause of migraines and can happen during menstrual cycles.

7. Cigarette Migraine

An equal opportunity source of migraines is because the nicotine alters blood vessels. High carbon monoxide levels in a person who smokes or even inhales second hand smoke can lead to a migraine.

8. Food Migraines Food allergies are another factor that leads to migraines. However, migraine sufferers are able to eat chocolate without falling prey to a migraine. Some patients actually report relief from eating chocolate.

Foods that Can Cause Migraines

1. Aged cheese such as Roquefort, Stilton and Sharp Cheddar

2. Fermented Dairy such as Sour Cream, Buttermilk and Yogurt

3. Citrus: Oranges or Grapefruit, including juice

4. Nuts: Peanuts, Walnuts or Pecans

5. Legumes: Peas, Beans and Soy product 6. Onions and Garlic

7. Bananas

8. Pickled foods: picked herring is the most common instigator

9. MSG found in Chinese food

10. Alcohol

Now that you know the common triggers, also note that skipping meals also causes migraines. Skipping meals causes your blood sugar to drop, which in turn causes a migraine.

Eight Ways to Kiss Your Migraine Goodbye

1. Medicine

Medicines have been used for centuries to treat migraines. Today Dr’s prescribe Beta Blockers to treat migraines by maintaining adequate dilation of blood vessels. Antidepressants: The brain chemical ‘serotonin’ plays a role in migraine attacks because the levels of serotonin may cause or relieve migraine and that’s why Drs sometimes prescribe antidepressants for migraines. Antidepressants reduce migraine frequency by regulating serotonin levels in the brain. Other drugs are triptans available as an injection or nasal spray. This type of drug shuts down the inflammation and transmission of migraine pain.

2. Surgical Treatment

Nerve stimulators have been used to control back and muscle pain and in 2003 a nerve stimulator was successfully used to treat chronic headaches. With nerve stimulation, one end of a wire is connected to a nerve that controls pain and the other is connected to a small battery powered generator. The patient controls the generator via a remote device. Once turned on, it disconnects the pain signal.

Not only do chronic migraine suffers face agonizing physical disabilities, they also have the psychological fear of not being able to earn a living or manage their home life because daily activities can suddenly become unbearable with the onset of a migraine.

3. Holistic Intervention

Rarely are people offered a non drug approach to treating migraines. Treating a migraine holistically not only can treat the migraine at onset but can also act as prevention.

Create a headache diary listing the 5 W’s.

A. Who were you with?

B. Where? Did someone irritate you? At work with glaring lights?

C. What? What medications were you on?

D. When? When did the headache start?

E. Why? Did some particular food or drink aggravate the situation? Did you get enough sleep?

4. Review your diary after 30 days and see if you can isolate the trigger.

5. Use heat to help dilate the blood vessels in the body. This must be done at direct onset of your migraine. Soak your hands in hot water for 20-30 minutes. As the migraine progresses and the blood vessels enlarge, apply ice to the back of the neck and forehead to help constrict capillaries that are pressing against the nerves.

6. Relaxation techniques

You can use relaxation techniques to manage stress. Research has found that people who consciously practice yoga daily for 30 – 45 minutes can learn to positively manipulate involuntary bodily responses like migraine pain. Studies have shown that relaxation practiced on a regular basis achieves a 45 to 80% reduction or elimination in both migraine severity and frequency. Yoga triggers a boost in the brain chemical serotonin, a neurotransmitter that is involved with your body’s anger, pain, sleep and migraine and can be a cure for headaches. Frequent headaches are a sign that you are stressed out and it’s your body’s way of saying slow down and take care of me. Especially if you are a type A personality. My type A patients often say they can’t sit still and have a difficult time with the relaxation/mediation part of yoga. My reply? What’s more difficult to live with. Meditating daily or living with a migraine, a stroke or a heart attack? These are very real situations that afflict people with constricted arteries and that’s why it’s vital that you make time for your health. Unfortunately for my patients, I often meet them after they’ve suffered from a condition of vascular abnormality. They are very motivated to participate because they have experienced what happens when blood flow to the heart or brain is compromised. Consequently they practice my techniques daily to reduce a recurrence. Why not make time now? There are 1440 minutes in a day. 45 minutes a day practicing yoga is a wise investment in your health that offers a positive life style with increased energy without the use of toxic drugs polluting your liver and fewer Doctor visits which equals fewer co-payments. Yoga Chi for Energy DVD includes medically engineered relaxation techniques with an 11 minute meditation by a crackling fireplace.



Butalbital Blog

Headaches are common pains that anyone can suffer. They can be caused by many factors such as stress, working for extended hours in front of the computer to injury and migraines which may be triggered by allergies such as food.

Whatever the cause may be, the fact remains that having a headache is very uncomfortable and may keep you from performing to your full potentials. One need not suffer so much because of it, especially if the problem is constant and may keep you from being productive. Headaches may come in different forms usually depending on the cause. So most definitely, before you could opt for any ways to get rid of your headache, you must know first what is causing it. The following are simple ways to get rid of headaches:

1. Maintain good posture and do some stretching. Poor posture while working can cause what are known as tension headaches. Staying in such a position for a very long time may cause the muscles of the neck and shoulders to tighten up. One way to get rid of this headache is to maintain a good posture while working. Every now and then or if you feel tension pains setting in, do some stretching to get rid of the headache before it gets worse.

2. Application of moist heat through a hot compress is also a good way to get rid of headaches. Get a towel and soak it in warm water and apply it on areas where you find pain and tension to rid your body of the discomfort.

3. In women, a common problem is headache that comes days before their period. This is usually felt as a pain directly behind the eyes. To get rid of this headache, women must eat foods that are rich in zinc, especially those that come from lean proteins such as lean meats.

4. Relax. The most common cause of headache is stress. Develop a healthy lifestyle which allows you to get enough sleep and rest. If you feel a huge headache coming in because of stress, get rid of this headache by taking a break from work and catching on some sleep.

5. Get a massage. Tension headaches, especially ones that come with pain that radiates through the neck and shoulders are extremely uncomfortable. A way to get of this headache is by getting some massage, especially on the scalp, neck and shoulder areas to release all the tension that have build up there.

6. Eat regularly. Do not skip meals because hunger and meal- skipping can also cause headaches. If you feel a headache about to start and you haven’t had anything to eat, take a break and grab a bite to prevent that headache from progressing further.

7. Drink lots of water. As much as possible, stick to the eight-glasses a day recommended amount of daily water intake. Water cools down the body and so when you feel a major headache, drink up to get rid of it.

8. Ice. Ice is known to be effective in relieving different types of pains, headaches included. So another option to get rid of your headache if to use ice. Lie down and have an ice pack placed on the areas where you feel pain and tension such as behind your neck, temples or forehead.

9. Kill the pain with pain killers. There are many over-the counter analgesics that are known to work for many forms of headaches. However, it is still best to consult a doctor first before choosing a pain reliever to get rid of your headache most especially if the problem persists for a very long time. It is best to work out with your doctor first what is truly causing the pain.

10. Watch what you eat. Some headaches are triggered by food. This is most especially true for migraine sufferers. So if you feel that your headache was prompted by something that you ate, stop eating that food and consult your doctor to determine whether this is truly the source of your headache.

Having a headache is an uncomfortable experience. It keeps you from performing your task and is counter-productive. Headaches have many causes and so to successfully get rid of that headache, it is best to try to figure out first what is causing it in the first place. Lifestyle still plays a major role in determining whether you headache problem is just temporary or will pester you for a very long time.



Fioricet blog, know more about fioricet

Introduction

The line “Change is must and change is accelerating” is very important in human life. There are several changes occur in each and every aspects of human civilization from the age of Homo erectus to today informational age. The main component of information age is computer which can stored a lot of information giving birth of a discipline namely Informatics. Informatics is Informatics is the discipline of science which investigates the structure and properties (not specific content) of scientific information, as well as the regularities of scientific information activity, its theory, history, methodology and organization. The science of informatics is applied indifferent field of science giving birth of different discipline namely Bioinformatics, Chemoinformatics, Geoinformatics, Health informatics, Laboratory informatics, Neuroinformatics, Social informatics.

The term “Chemoinformatics” appeared a few years ago and rapidly gained widespread use. Workshops and symposia are organized that are exclusively devoted to chemoinformatics, and many job advertisements can be found in journals. The first mention of chemoinformatics may be attributed to Frank Brown.

The use of information technology and management has become a critical part of the drug discovery process as well as to solve the chemical problems. So, chemoinformatics is the mixing of those information resources to transform data into information and information into knowledge for the intended purpose of making better decisions faster in the area of drug lead identification and organization.

Whereas we see here chemoinformatics focused on drug design. Greg Paris came up with a much broader definition Chemoinformatics is a generic term that encompasses the design, creation, organization, management, retrieval, analysis, dissemination, visualization, and use of chemical information. Clearly, the transformation of data into information and of information into knowledge is an endeavor needed in any branch of chemistry not only in drug design. The view that chemoinformatics methods are needed in all areas of chemistry and adhere to a much broader definition:

chemoinformatics is the application of informatics methods to solve chemical problems.

Why do we have to use informatics methods in chemistry?

First of all, chemistry has produced an enormous amount of data and this data avalanche is rapidly increasing. More than 45 million chemical compounds are known and this number is increasing by several millions each year. Novel techniques such as combinatorial chemistry and high-throughput screening generate huge amounts of data. All this data and information can only be managed and made accessible by storing them in proper databases. That is only possible through chemoinformatics.

On the other hand, for many problems the necessary information is not available. We know the 3D structure, determined by X ray crystallography for about 300,000 organic compounds. Or, as another point, the largest database of infrared spectra contains about 200,000 spectra. Although these numbers may seem large, they are small in comparison to the number of known compounds: We know from less than 1% of all compounds their 3D structure or have their infrared spectra. The question is then; can we gain enough knowledge from the known data to make predictions for those cases where the required information is not available?

There is another reason why we need informatics methods in chemistry: Many problems in chemistry are too complex to be solved by methods based on first principles through theoretical calculations. This is true, for the relationships between the structure of a compound and its biological activity, or for the influence of reaction conditions on chemical reactivity.

All these problems in chemistry require novel approaches for managing large amounts of chemical structures and data, for knowledge extraction from data, and for modeling complex relationships. This is where chemoinformatics methods can come in.

The representation of the chemoinformatics in graphical form is given below.

Source: authors

Extracting knowledge from chemical information -lots of data (structure, activities, genes, etc) i.e. called as inductive learning. When we extract data from knowledge, it is called as deductive learning.

Is it Cheminformatics or Chemoinformatics?

The name of our favourite field maybe cheminformatics or chemoinformatics chemiinformatics, molecular informatics, chemical informatics, or even chemobioinformatics. All these options have some advantages. By using short cheminformatics you are saving the keyboard of your computer, chemoinformatics sounds nice in sentences like “… our software solution seamlessly integrates chemoinformatics and bioinformatics …”, and the title “Head of chemobioinformatics” on a business card cannot miss the point. Molecular informatics or chemical informatics is less known, but this also means that you are one of the pioneers on the forefront of a new scientific field. But the name of chemoinformatics and cheminformatics are synonymous in use. In the following table frequencies of words cheminformatics and chemoinformatics in web pages are listed, as determined by a popular search engine Google. The ratio characterizes popularity of term cheminformatics over chemoinformatics.

Year Cheminformatics Chemoinformatics Ratio

2000 39 684 0.05

2001 8,010 2,910 2.75

2002 34,000 16,000 2.12

2203 58,143 32,872 1.77

2204 85,435 60,439 1.41

2005 6,58,298 2,72,096 2.41

2006 3,17,000+ 1,63,000+ 1.94

Source: Leach AR. et.al. (2003)

History of Chemoinformatics

The first, and still the core, journal for the subject, the Journal of Chemical Documentation, started in 1961 (the name Changed to the Journal of Chemical Information and computer Science in 1975). Then the first book appeared in 1971 (Lynch, Harrison, Town and Ash, Computer Handling of Chemical Structure Information). The first international conference on the subject was held in 1973 at Noordwijkerhout and every three years since 1987. The term Chemoinformatics was given by Brown in 1998.

With all the problems at hand in chemistry, complex relationships, profusion of data, lack of necessary data, quite early on the need was felt in many areas of chemistry to have resort to informatics methods. These various roots of chemoinformatics often go back more than 40 years into the 1960s.

1. Chemical Structure Representation

In the early sixties, various forms of machine readable chemical structure representations were explored as a basis for building databases of chemical structures and reactions. Eventually, connection tables that represent molecules by lists of the atoms and of the bonds in a molecule gained universal acceptance. Connection tables were also used for the Chemical Abstracts Registry System which appeared in the second half of the sixties.

A connection table stores the same information that is present in a 2D structure diagram, namely the atoms that are present in a molecule and what bonds exist between the atoms. However, it is stored in a table form which is much easier for a computer to work with. Before a connection table is produced, the atoms in the molecule must be numbered, and an atom lookup table produced. This simply stores atom information (usually just the atom type) cross referenced with the atom number. Here is a numbering and atom lookup table for acetaminophen:

Num Atom

Type

1 C

2 C

3 C

4 N

5 C

6 O

7 C

8 C

9 C

10 C

11 O

Source: authors

The atom lookup table describes the atoms present in a molecule, but says nothing about how they are connected.

The connection table describes how atoms are connected by bonds, and has a row and a column for each atom, the row and column number representing the number given to the atom.

Source: authors

For example, if a bond exists between atom 5 and atom 8, then a “1” is placed at the intersection of row 5 and column 8 (and also row 8 and column 5), otherwise a 0 is placed at the intersection. Further, we may use a 2 to represent a double bond, 3 to represent a triple bond, and so on. Here is the connection table for Acetaminophen, along with the diagram showing which numbers correspond to which atoms.

For clarity, the non-zero entries are showing in bold. Note how the table is symmetrical about the diagonal from top left to bottom right. This will always be the case since, for example, if atom 3 is bonded to atom 2, then atom 2 is also by definition bonded to atom 3. Since this connection table effectively stores each piece of information twice, it is called a redundant connection table. Normally, we just store one half of the table in a non-redundant connection table as shown below:

Source: authors

2. Structure Searching

This involves searching a database for an exact match with a specified query structure. For example, if the following is the query.

Then only an exact match to this structure would be returned by a search. The techniques used to perform the search won’t be covered here, but basically they involve treating the 2D connection table as a mathematical graph, where the nodes represent atoms and the edges represent bonds, and then a test for exact match can be done using a graph isomorphism algorithm (a standard computer science technique).

A connection table is essentially a representation of the molecular graph (A graph is a mathematical conceptualization of anything that consists of connected points).Therefore, for storing a unique representation of a molecule and for allowing its retrieval, the graph isomorphism problem had to be solved to define from a set of potential representations of a molecule a single one as the unique one.

The first solution was the Morgan algorithm for numbering the atoms of a molecule in a unique and unambiguous manner. By Morgan algorithm atoms of the same elemental type can be topologically equivalent or not is judged. Let us label the carbons C, CH and CH1H2, and the hydrogens H, H1 and H2. Obviously, only atoms of the same elemental type can be topologically equivalent. Thus, it is immediately clear that the carbon atoms can be separated from the hydrogen atoms.

The algorithm proceeds by analyzing the extended connectivity in the following way. A score is assigned to each atom. Initially, the scores are computed by counting the number of bonds formed by each atom: i.e. C = 1, CH = 3 and CH1H2 = 3. This tells us that C is unique; hence, amongst the carbons, only CH and CH1H2 can possibly be topologically equivalent. All the hydrogens have a score (i.e. sum connectivity) of 1. In the second iteration, the new score of each atom is calculated by summing the first-iteration scores of all the atoms to which it is bonded. CH gets a score of 1 (C) + 1 (H) + 3 (CH1H2) = 5. CH1H2 gets a score of 3 (CH) + 1 (H1) + 1 (H2) = 5. H gets a score of 3. H1 and H2 also get scores of 3. Scores based on summing the atomic numbers of bound atoms are also computed: CH gets a score of 13, CH1H2 gets a score of 8 and the protons all score 6. This means that CH is distinct from CH1H2. In the third cycle of iteration, the scores based on numbers of bonds become 5 for all the protons, but the scores based on atomic numbers become 13 for H, and 8 for H1 and H2. Thus, H is distinct from H1 and H2.The termination criterion for the iterative process is when no further atoms can be assigned as unique by an iteration. At this point, we know which atoms are grouped together: those that had the same score at each iteration are topologically equivalent. In this example, the fourth pass shows that H1 and H2 are equivalent. This provided the basis for full structure searching. Then, methods were developed for substructure searching, for similarity searching, and for 3D structure searching.

Substructure searching

A substructure search involves finding all the structures in a database that contain one or more particular structural fragments. For example, we might want to find all of the structures in a database which contain the nitro group:

Substructure searching requires some method of specifying a query (i.e., we want to find this and that, but not this, etc). One popular example is SMARTS, an extension to SMILES. Mathematically, substructure searching is performed, as with structure searching, using a graph representation, but this time a subgraph isomorphism algorithm finds occurrences of subgraphs (i.e. substructures) in a structure.

Similarity searching

Similarity searching involves looking for all the structures in a database that are highly similar to a given structure. The most common use is to find compounds that could exhibit similar properties (based on the similar property principle that compounds with similar structures are likely to exhibit similar biological behaviors). Note that “similarity” is a subjective thing. As an example, a similarity search might involve looking for structures with a similarity greater than 0.7 to this molecule

Obviously some method is required for measuring similarity. This is usually done using fingerprint representations and similarity coefficients as described below, which are used in various applications that involve measurement of similarity, for example cluster analysis.

Fingerprint representations

A fingerprint characterizes the 2D structure of a molecule, usually through a string of ‘1’s and ‘0’s. There are two basic types of fingerprint: structural keys and hashed fingerprints.

Structural Keys -Structural keys contain a string of bits (‘1’s and ‘0’s) where each bit is set to 1 or 0 depending on the presence or absence of a particular fragment. They usually employ a pre-defined dictionary of fragments.

Hashed fingerprints- In hashed fingerprints, there is no set dictionary or 1:1 relationship between bits and features. All possible fragments in a compound are generated. The number of fragments represented can be huge. Thus rather than assigning one bit position for each fragment, the bits are “hashed” down onto a fixed number of bits. Thus hashed fingerprints are a less precise form, but they carry more information.

Once fingerprint representations are available, similarity coefficients can be used to give a measure of similarity between two fingerprints.

3. Quantitative Structure Activity / Property Relationship (QSAR/QSPR)

Building on work by Hammett and Taft in the fifties, Hansch and Fujita showed in 1964 that the influence of substituents on biological activity data can be quantified.

In the last 40 years, an enormous amount of work on relating descriptors derived from molecular structures with a variety of physical, chemical, or biological data has appeared. These studies have established Quantitative Structure-Activity Relationships (QSAR) and Quantitative Structure-Property Relationships (QSPR) as fields of their own, with their own journals, societies, and conferences.

Percent Spikelet Sterility (% Ss) of N-acylanilines Tested in Winter 2001-02 at 1500 ppm Spray Concentrations on PBW 343

Source: Gasteiger J. et.al. (2006)

Modern QSAR involves applying artificial intelligence and Statistical techniques to 2D or 3D molecular representations.

SAR Application

Source: R. K. Lindsay et. al. (1980).

At the time of drug design, we have to look after these following points-

• Single therapeutic target

• Drug like chemical

• Some toxicity anticipated

• Multiple unknown targets

• Diverse Structures

• Human and ecosystems

4. Chemometrics

Initially, the quantitative analysis of chemical data relied exclusively on multilinear regression analysis. However, it was soon recognized in the late sixties that the diversity and complexity of chemical data need a wide range of different and more powerful data analysis methods. Pattern recognition methods were introduced in the seventies to analyze chemical data. In the nineties, artificial neural networks gained prominence for analyzing chemical data. The growing of this area led to the establishment of chemometrics as a discipline of its own with its own society, journals, and scientific meetings.

Source: R. K. Lindsay et. al. (1980).

An artificial neural network (ANN) or commonly just neural network (NN) is an interconnected group of artificial neurons that uses a mathematical model or computational model for information processing based on a connectionist approach to computation.

5. Molecular Modeling

In the late sixties, R. Langridge and coworkers developed methods for visualizing 3D molecular models on the screens of Cathode Ray Tubes. At the same time, G. Marshall started visualizing protein structure on graphic screens. The progress in hardware and software technology, particularly as concerns graphics screens and graphics cards, has led to highly sophisticated systems for the visualization of complex molecular structures in great detail. Programs for 3D structure generation, for protein modeling, and for molecular dynamics calculations have made molecular modeling a widely used technique. The commonly available softwares for molecular modeling are ArgusLab, Chimera, and Ghemical.

6. Computer-Assisted Structure Elucidation (CASE)

The elucidation of the structure of a chemical compound, be it a reaction product or a compound isolated as a natural product, is one of the fundamental tasks of a chemist. Structure elucidation has to consider a wide variety of different types of information mostly from various spectroscopic methods, and has to consider many structure alternatives. Thus, it is an ambitious and demanding task. It is therefore not surprising that chemists and computer scientists had taken up the challenge and had started in the 1960?fs to develop systems for computer-assisted structure elucidation (CASE) as a field of exercise for artificial intelligence techniques. The DENDRAL project, initiated in 1964 at Stanford University gained widespread interest.

Other approaches to computer-assisted structure elucidation were initiated in the late sixties by Sasaki at Toyohashi University of Technology and by Munk at the University of Arizona.

7. Computer-Assisted Synthesis Design (CASD)

The design of a synthesis for an organic compound needs a lot of knowledge about chemical reactions and on chemical reactivity. Many decisions have to be made between various alternatives as to how to assemble the building blocks of a molecule and which reactions to choose. Therefore, computer-assisted synthesis design (CASD) was seen as a highly interesting challenge and as a field for applying artificial intelligence techniques. In 1969 Corey and Wipke presented their seminal work on the first steps in the development of a synthesis design system. Nearly simultaneously several other groups such as Ugi and coworkers, Hendrickson and Gelernter reported on their work on CASD systems. Later also at Toyohashi work on a CASD system was initiated.

Basics of Chemoinformatics

The various fields outlined in the previous section have grown from humble beginnings 40 years ago to areas of intensive activities. On top of that it has been realized that these areas share a large number of common problems, rely on highly related data, and work with similar methods. Thus, these different areas have merged to a discipline of its own: Chemoinformatics.

Figure 1. The various areas of activities in chemoinformatics

Source: Lipinski, C.A et.al., (1997)

The extent of this field has recently been documented by a “Handbook of Chemoinformatics”, covering 73 contributions by 65 scientists on 1850 pages in four volumes. The following gives an overview of chemoinformatics, emphasizing the problems and solutions – common to the various more specialized subfields.

1. Representation of Chemical Compounds

A whole range of methods for the computer representation of chemical compounds and structures has been developed: linear codes, connection tables, matrices. Special methods had to be devised to uniquely represent a chemical structure, to perceive features such as rings and aromaticity, and to treat stereochemistry, 3D structures, or molecular surfaces. Earlier the chemical 2D structure representations are done by software namely Chemdraw, ISIS etc. But now, chemical structures are represented by molecular graph. A graph is an abstract structure that contains nodes connected by edges. Here nodes are represented by atoms and edges by bonds. A graph represents only topology of a molecules i.e. the ways the nodes i.e. atoms are connected.

Aspirin

Source: J. Zupan et.al.,(1999).

The aspirin structure can be represented by Graph theory, where Oxygen atom is represented by filled bullet and carbon atom is represented by vacant bullet and hydrogen atom is not represented here. So, the aspirin structure will be-

For similarities searching we can use the graph isomorphism or by any algorithm.

Linear notations

Structure linear notations convert chemical structure connection tables to a string, a sequence of letters, using a set of rules. The earliest structure linear notation was the Wiswesser Line Notation (WLN). ISI® adopted WLN to be used in some of their products in 1968 and, it is still use today. It was also adopted in the mid 1960s for internal use by many pharmaceutical companies. At that time (mid 60s to 80s), it was considered the best tool to represent, retrieve and print chemical structures. In WLN, letters represents structural fragments and a complete structure is represented as a string. This system efficiently compressed structural data and, was very useful to storing and searching chemical structures in low performance computer systems. However, the WLN is difficult for non- experts to understand. Later, David Weininger suggested a new linear notation designated as SMILESTM. Since SMILESTM is very close to the “natural language” used by organic chemists, SMILESTM is widely accepted and used in many chemical database systems. To successfully represent a structure, a linear notation should be canonicalized. That is, one structure should not correspond to more than one linear notation string, and conversely, one linear notation string should only be interpreted as one structure.

Attempt to condense all of the connectivity information into a single text string. The two most popular formats are SMILES (from Daylight) and SLN (Tripos format inspired by SMILES).

SMILES (Simplified Molecular Input Line Entry Specification)

Acetaminophen

In SMILES, atoms are generally represented by their chemical symbol, with upper-case representing an aliphatic atom (C = aliphatic carbon, N = aliphatic nitrogen, etc) and lower-case representing an aromatic atom (c = aromatic carbon, etc). Hydrogens are not normally represented explicitly. Consecutive characters represent atoms bonded together with a single bond. Therefore, the SMILES for propane would simply be: CCC or 1-propanol would be: CCCO. Double bonds are represented by an “=” sign, e.g. propene would be: C=CC. Parentheses are used to represent branching in the molecule, e.g. the SMILES for Isopropyl alcohol (2-propanol) is: CC(O)C. Atoms other than the major organic ones (C, S, N, O, P, Cl, Br, I, B) or ions must be enclosed in square brackets. Ring enclosures are represented by using numbers to signify attachment points, usually starting at 1. The first occurrence of the number defines the attachment point, and subsequent occurrences indicate that the structure joins back to the attachment point at that position. For example, the SMILES for Benzene is as follows (note the small ‘c’ for aromatic carbon): c1ccccc1. We can also use branching from the ring system, e.g.

c1cc(Br)ccc1 represents bromobenzene. Note that in many cases there can be several SMILES to represent the same structure – for example, we could alternatively represent bromobenzene as: c1cccc(Br)c1. So here is a SMILES representation for acetaminophen, the structure at the top of this document: c1c(O)ccc(NC(=O)C)c1. The great advantage of these methods is brevity – for example an entire SMILES string can be stored in a single spreadsheet cell. However, it is hard to add additional information (coordinates, properties, etc) in these formats in an elegant way.

Canonicalization

If a structure corresponds to a unique WLN or a unique SMILESTM string, then the structure search results in a string match. WLN could meet this requirement in most cases. The SMILESTM approach can do this after canonical processing. Therefore, both WLN and canonical SMILESTM are able to solve structure search problems by string matches. A molecular graph (2D structure) can also be canonicalized into a real number through a mathematical algorithm. The real number is identified as a molecular topologic index. However, two different structures can have the same topologic index. Therefore, topologic indices can only be used as screens for accelerating structure database searching. Actually, the concept of molecular index was originally proposed for QSAR and QSPR studies. Wiener reported the first molecular topological index in 1947 [25]. If a molecule and its specific topologic index had a one-to-one relationship, then structure search could be done by number comparison [25]. However, substructure search still had to use an atom-by-atom matching algorithm, which, as mentioned earlier, could be very time-consuming. In order to further enhance chemical database search performance, efforts have been on the way to seek better structural screening technologies.

Sources of 3d informations and the Representation of molecules in 3D Form.

3D information can be obtained through X-ray crystallography, NMR spectroscopy or by computational means. The basic forms of 3D representation are the coordinate table and the distance matrix.

A coordinate table is simply an extension of the atom lookup table that also contains coordinates for each atom. These coordinates are relative to a consistent origin. Here is a sample coordinate table for Aspirin, along with a 3D structure with the atoms numbered:

Source: Gasteiger, J., (2003)

Distance matrices are similar to connection tables, except that instead of storing connectivity information, they store relative distances (in Angstroms) between all atoms.

Here is a sample distance matrix for the Aspirin molecule above. Many pattern recognition techniques require distance or similarity measurements to quantitatively measure the distance or similarity of two objects (in our case, the objects are small molecules). Euclidean distance, Mahalanobis distance and correlation coefficients are commonly used for distance measurement,

where n is the number of descriptors, D represents the absolute distance between A and B, R represents the angle of vectors A and B in multidimensional space and, is interpreted as the quantity of the linear correlation of A and B. The value range of R is between –1 to +1 that is, from 100% dissimilar to 100% similar. The Euclidian distance assumes that variables are uncorrelated. When variables are correlated, the simple Euclidean distance is not an appropriate measure, however, the Mahalanobis distance (2) will adequately account such correlations. The Tanimoto coefficient is commonly employed for similarity measurements of bit-strings of structural fingerprints (Boolean logic). The simplified form is

where ? is the count of substructures in structure A, ? the count of substructures in structure B, and ? is the count of substructures in both A and B. Many different similarity calculations have been reported. Holliday, Hu and Willett have published a comparison of 22 similarity coefficients for the calculation of inter-molecular similarity and dissimilarity, using 2D fragment bit-strings [51].

Source: Gasteiger, J., (2003)

Distance matrices are useful when comparing molecules with each other, whereas coordinate tables tend to be used for structure visualization.

2. Representation of Chemical Reactions

Chemical reactions are represented by the starting materials and products as well as by the reaction conditions. On top of that, one also has to indicate the reaction site, the bonds broken and made in a chemical reaction. Furthermore, the stereochemistry of reactions has to be handled. Searching databases of reactions is a little different to straight searching, although the kinds of search are the same (structure, substructure, similarity). However, searching may be done on reactants, products, or both, and searches may be performed for entire reactions (as opposed to single structures). Representation of reactions is by the usual means (connection tables, atom lookup tables), but with additional information about which molecules are products and reagents, and which reagent atoms map to which product atoms. A derivative of SMILES, called Reaction SMILES is available for representing reactions, along with a way for defining reaction queries called SMIRKS.

3. Data in Chemistry

Much of our chemical knowledge has been derived from data. Chemistry offers a rich range of data on physical, chemical, and biological properties: binary data for classification, real data for modeling, and spectral data having a high information density. These data have to be brought into a form amenable to easy exchange of information and to data analysis

4. Datasources and Databases

The enormous amount of data in chemistry has led quite early on to the development of databases to store and disseminate these data in electronic form. Databases have been developed for chemical literature, for chemical compounds, for 3D structures, for reactions, for spectra, etc. The internet is increasingly used to distribute data and information in chemistry. The databases of virtual molecules are available now i.e. the molecules which are not present in the nature, but by just virtually we can prepare databases with the help of databases of other molecules. The commonly available softwares for databases are Amicbase, Asinex Gold, Cheminformatics.org, FDA MRTD, NCI, Otava Dataset, PubChem, and ZINC.

5. Structure Search Methods

In order to retrieve data and information from databases, access has to be provided to chemical structure information. Methods have been developed for full structure, for substructure, and for similarity searching. Those are discussed in above.

6. Methods for Calculating Physical and Chemical Data

A variety of physical and chemical data of compounds can directly be calculated by a range of methods. Foremost are quantum mechanical calculations of various degrees of sophistication. However, simple methods such as additive schemes can also be used to estimate a variety of data with reasonable accuracy.

7. Calculation of Structure Descriptors

In most cases, however, physical, chemical, or biological properties cannot be directly calculated from the structure of a compound. In this situation, an indirect approach has to be taken by, first, representing the structure of the compound by structure descriptors, and, then, to establish a relationship between the structure descriptors and the property by analyzing a series of pairs of structure descriptors and associated properties by inductive learning methods. A variety of structure descriptors has been developed encoding 1D, 2D, or 3D structure information or molecular surface properties. The manipulation and analysis of chemical structure information is made through the molecular structure descriptors. These are the numerical values which characterizes propertities of molecules. They may represents the physiochemical properties of a molecule or may b the values derived from the algorithm technique to the chemical structures. For example, the molecular weight does not represent the whole properties of a molecule but it is very quick. In case of quantum molecular based structure descriptors, it tells about the properties of a molecule but it is time consuming.

The commonly used molecular descriptors are logP and molar refractivity. Hydrophobicity is most commonly modeled using the logarithm values of partition coefficient i.e. logP.

8. Data Analysis Methods

A variety of methods for learning from data, of inductive learning methods is being used in chemistry: statistics, pattern recognition methods, artificial neural networks, genetic algorithms. These methods can be classified into unsupervised and supervised learning methods and are used for classification or quantitative modeling. The softwares are using in data analysis & statistics are ChemTK Lite, PowerMV, & GCluto.

Chemistry Based Data Mining and Exploration

For synthesis a molecule, first we have to search data with the help databases available for that molecule, then we have to search the database available for structure analogue. Now the Structure activity relationships are studied and different biological or mechanistic analogue are synthesized. The scheme is given in below……

Applications of Chemoinformatics

a.Fields of Chemistry

The range of applications of chemoinformatics is rich indeed; any field of chemistry can profit from its methods. The following lists different areas of chemistry and indicates some typical applications of chemoinformatics. It has to be emphasized that this list of applications is by far not complete!

1. Chemical Information

o storage and retrieval of chemical structures and associated data to manage the flood of data by the softwares are available for drawing and databases.

o dissemination of data on the internet

o cross-linking of data to information

2. All fields of chemistry

o prediction of the physical, chemical, or biological properties of compounds

3. Analytical Chemistry

o analysis of data from analytical chemistry to make predictions on the quality, origin, and age of the investigated objects

o elucidation of the structure of a compound based on spectroscopic data

4. Organic Chemistry

o prediction of the course and products of organic reactions

o design of organic syntheses

5. Drug Design as well as for bioactive molecules.

o identification of new lead structures

o optimization of lead structures

o establishment of quantitative structure-activity relationships

o comparison of chemical libraries

o definition and analysis of structural diversity

o planning of chemical libraries

o analysis of high-throughput data

o docking of a ligand into a receptor

Finally, small molecules can be used for docking and drug screening/discovery. Small molecules, as well as their synthetic derivatives, can be docked to a protein target and computationally filtered (e.g. by solubility) to produce a ranked list of candidates that can then be tested in the laboratory. Known ligands can also be used in similarity searches, or as scaffold for further molecular engineering. We will present several recent drug discovery efforts that leverage ChemDB and the computational tools described above. In particular, the discovery of several compounds has done that can bind to the Carboxyltransferase domain of Acyl-CoA Carboxylase, AccD5 from Mycobacterium tuberculosis:, a new TB therapeutic target.

o prediction of the metabolism of xenobiotics

o analysis of biochemical pathways

o Modeling of ADME-Tox properties.

Historically, drug absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies in animal models were performed after a lead compound was identified. Now, pharmaceutical companies are employing higher-throughput, in vitro assays to evaluate the ADMET characteristics of potential leads at earlier stages of development. This is done in order to eliminate candidates as early as possible, thus avoiding costs, which would have been expended on chemical synthesis and biological testing. Scientists are developing computational methods to select only compounds with reasonable ADMET properties for screening. Molecules from these computationally screened virtual libraries can then be synthesized for high-throughput biological activity screening. As the predictive ability of ADME/Tox software improves, and as pharmaceutical companies incorporate computational prediction methods into their R&D programs, the drug discovery process will move from a screening based to a knowledge-based paradigm. Under multi-parametric optimization drug discovery strategies, there is no excuse for failing to know the relative solubility and permeability rankings of collections of chemical compounds for lead identification.

a. Absorption. Passive intestinal absorption (PIA) models have been studied by many groups, for years. The fluid mosaic model holds that the structure of a cell membrane is an interrupted phospholipid bilayer capable of both hydrophilic and hydrophobic interactions. Trans cellular passage through the membrane lipid/aqueous environment is the predominant pathway for passive absorption of lipophilic compounds, while low-molecular-weight (300) of molecular descriptors (constitutional, topological, geometrical, electrostatic, quantum-chemical and thermodynamic) calculated using quantum-chemical semi empirical methodology.

Chemo bioinformatics

Biochemoinformatics (or chemobioinformatics) is a new term to describe the research efforts on meeting the emerging needs for the integration of bioinformatics and chemoinformatics. Historically, bioinformatics and chemoinformatics have largely evolved independently from biology and chemistry. Generally speaking, bioinformatics deals with biological information, which although traditionally refers to sequences information on large biological molecules such as DNA, RNA and proteins, also refers to the more recent emergence of micro array data on gene and protein expression.

Chemoinformatics on the other hand mainly deals with chemical information of drug-like small molecules, the molecular weight of these being several hundred Daltons. The elemental data record in bioinformatics is centered on genes and their products (RNA, protein, and so on), whereas the fundamental data type in chemoinformatics is centered on small molecules.

Source: Drews,J.,(2000)

Key challenges

The key challenge for computational methods then is not traveling through chemical space per se, but rather to be able to focus traveling expeditions in a vast chemical space towards interesting regions, and to be able to recognize interesting stars and galaxies when they are encountered. The notion of what is interesting may vary of course with the task (e.g. drug discovery, reaction discovery, polymer discovery). But at the most fundamental level what is needed are tools to predict the physical, chemical, and biological properties of small molecules and reactions in order to focus searches and filter search results. Computational methods in chemistry can be organized along a spectrum ranging from Schrodinger equation, to molecular dynamics, to statistical machine learning methods. Quantum mechanical methods, or even molecular dynamics methods, are computationally intensive and do not scale well to large datasets. These methods are best applied to specific questions on focused small datasets. Statistical and machine learning methods are more likely to yield successful approaches for rapidly sifting through large datasets of chemical information. Because in the absence of large public database and datasets, chemoinformatics is in a state reminiscent of bioinformatics two or three decades ago, it may be productive to adapt the lessons learnt from bioinformatics to chemoinformatics, while maintaining also a perspective on the fundamental differences between these two relatively young interdisciplinary sciences. If this analogy is correct, two key ingredients were essential for unlocking the large-scale development of bioinformatics and the application of modern statistical machine learning methods to biological data, data and similarity measures. In bioinformatics, such as Genbank, Swissprot, and the PDB while alignment algorithms have provided robust similarity measures with their fast BLAST implementation becoming the workhorse of the field. Mutatis mutandis, the same is likely to be true in chemoinformatics.

This new drug discovery strategy, challenges cheminformatics in the following aspects: (1) cheminformatics should be able to extract knowledge from large-scale raw HTS databases in a shorter time periods, (2) cheminformatics should be able to provide efficient in silico tools to predict ADMET properties,

Conclusions

Chemoinformatics has developed over the last 40 years to a mature discipline that has applications in any area of chemistry. Chemoinformatics is the science of determining those important aspects of molecular structures related to desirable properties for some given function. One can contrast the atomic level concerns of drug design where interaction with another molecule is of primary importance with the set of physical attributes related to ADME, for example. In the latter case, interaction with a variety of macromolecules provides a set of molecular filters that can average out specific geometrical details and allows significant models developed by consideration of molecular properties alone. The field has gained so much in importance that the major topics of chemoinformatics have to be integrated into chemistry curricula, a few universities have to offer full chemoinformatics curricula to satisfy the urgent need for chemoinformation specialists. There are still many problems that await a solution and therefore we still will see many new developments in chemoinformatics.

References

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Brown F.K. (1998), Chemoinformatics: What is it and how does it Impact? Drug Discovery Ann. Reports Med. Chem., 33:375-384.

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Xu J. and Hagler A. (2002) Chemoinformatics and Drug Discovery, Molecules, 7: 566-600



Acetaminophen

At one point or another each of us has experienced pain.

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If you or someone you care about suffers from chronic pain, there really is something you can do about it.

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Many people use acetaminophen and ibuprofen for pain relief. There are so many side effects associated with long term use of these remedies who want to take that kind of a risk. Side effects such as liver failure with acetaminophen and gastric upset and bruising with ibuprofen. Recently there was a report released about the use of acetaminophen long term and it was not pretty. Wouldn’t it be best to look for long term answers to osteoarthritis instead of just treating the symptoms.

As a registered nurse, I believe that arthritis knee pain should be treated by natural means. Treating the underlining cause of the disease is the best method because not only are your the treating the symptoms naturally but you are correcting the cause as well.

For instance, we know that osteoarthritis is a result of damage knee cartilage from wear and tear in the joints. As we age, we lose the ability to produce natural substances our body need to rebuild cartilage such as glycosaminoglycans. Glycosaminoglycans is a major component for joint cartilage reproduction and if you never heard of glycosaminoglycans don’t worry about it. Damaged knee cartilage becomes more and more deteriorated and degenerative if we can not produce this substance in adequate amounts.

So let focus on natural supplements that help rebuild and support healthy cartilage. As a result, when you support and nourish cartilage, this in turn reduce arthritis knee pain and promote healthy joints. To accomplish this goal, what are the best natural supplements out there?

Glucosamine and MSM(Methylsulfonylmethane) are two naturally supplements that can be taken for arthritis knee pain. They help support, rebuild and nourish cartilage and connective tissues. This process of nourishing and rebuilding cartilage is important to long term relief of arthritis knee symptoms.

The key to finding the best natural product to choose from is finding one that uses natural ingredients that work together synergistically because you just don’t want another salve, juice or pill that just don’t work. The most important thing for you is that you don’t have to let arthritis knee pain slow you down with the proper natural supplements there is help.



Buy Tramadol

A few years back, muscle relaxants have taken center stage after several reports of deaths due to abuse of the drug, prompting concerned agencies to take cognizant of the issue.

A hospital staff was charged for murdering six elderly hospital patients by giving those overdoses of two muscle relaxants in 1996 and 1997. The suspect used muscle relaxants Pavulon and succinylcholine chloride, commonly known as SUCC — to shut down the respiratory systems of the patients, essentially suffocating them.

In another incident, Raplon, another popular muscle relaxant was voluntarily withdrawn by its manufacturer from the market after five reported deaths related to its use. Doctors often use Raplon when inserting a breathing tube in patients, and it is a good choice because of the drug’s effectiveness wore off quickly. Despite its benefits, Raplon was pulled from the market because it tends to cause airway spasms that interfere with normal breathing.

The US Food and Drug Administration (FDA) were already aware of this side effect, especially since most muscle relaxants can cause similar problems. Called bronchospasms, the breathing problem can range from mild to severe and is noted to occur in 3.2 percent of all patients who use Raplon.

Raplon is the twelfth drug removed from the market since 1997. This is causing a bit of a stir, with many people questioning the FDA’s rapid approval of drugs. The FDA has been under pressure from Congress to speed up the approval times of new drugs.

But law makers and consumers would not want quality and safety to be sacrificed for a fast approval time. Though the demands of new drugs are indeed high, the FDA should always keep a keen eye on the effects and effectiveness of these drugs. Once the drug is approved and sold in the market, recall would take more effort especially when some lives have already been wasted.

Muscle Relaxants

Skeletal muscle relaxants are a heterogeneous group of medications commonly used to treat two different types of underlying conditions namely spasticity from upper motor neuron syndromes and muscular pain or spasms from peripheral musculoskeletal conditions.

Although they have by convention been classified into one group, the FDA has approved only a few medications in this class for treatment of

spasticity; the remainder are approved for treatment of musculoskeletal conditions.

Data from the Third National Health and Nutrition Examination (NHANES III) survey (1988-1994) estimated that 1% of American adults are taking muscle relaxants, often on a chronic basis.

Spasticity, although difficult to define precisely, is a clinical condition that has been described as a motor disorder characterized by velocity dependent increase in tonic stretch reflexes or muscle tone. This also goes with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex, as one component of the upper motor neuron syndrome.

Some of the more common conditions associated with spasticity and requiring treatment include multiple sclerosis, spinal cord injury, traumatic brain injury, cerebral palsy, and post-stroke syndrome.

Common musculoskeletal conditions causing tenderness and muscle spasms include fibromyalgia, tension headaches, myofascial pain syndrome, and mechanical low back or neck pain. If muscle spasm is present in these conditions, it is related to local factors involving

the affected muscle groups.

This type of drug is said to relax certain muscles in the body and relieve the stiffness, pain and discomfort caused by strains, sprains or other injury to your muscles. However, these medicines do not take the place of rest, exercise or physical therapy, or other treatment that your doctor may recommend for your medical problem.

The Aftermath

Since the relaxants act in the central nervous system, their actions may produce some side effects. In the U.S., dispensing of muscle relaxants without doctor’s prescription is strictly prohibited but in other countries, some muscle relaxants can be sold without prescription.

With the many reported abuse and deaths using muscle relaxants, patients have become cautious. Likewise concerned government agencies continue to monitor the dispensing of these drugs to avoid further loss on human lives.

Controversies surrounding muscle relaxants have resulted in some resistance to their use in patient care. Studies have been published which suggest a potential role for muscle relaxants in clinical practice; however, there is a lack of good quality research on the clinical application of these drugs.

It cannot be denied that muscle relaxants are effective in the management of a number of ailments but the adverse effects require that they be used with caution.





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