Saturday, September 25, 2010

(In)famous histamine


Histamine, called by the chemists 2-(imidazol-4-yl)ethylamine, is located in many tissues of the body and even if its physiological function is too complex to be currently, completely understood, sure is that histamine plays a predominant role in the allergic inflammatory response of the body and in the regulation of the secretion of gastric acid.
Therefore, a huge effort has been done to the development of drugs (medicaments) that antagonize (stop) its effects and therefore reduce the allergic reaction of the body and/or help to the regulation of the gastric acid.
For a compound to have effect in the body, it has to interact in one way or another with the metabolic pathways. Usually this interaction happens between the compound, usually a small molecule (in this case histamine) and a big molecule, a protein (or an enzime, which are just a specialized kind of proteins).
The target protein is called receptor, and associated to the name of the small moleculle which is able to interact with it, therefore the proteins in the metabolic pathways which interact with the histamine moleculle are called histamine receptors.
In general, the receptors, these proteins, are inside of the body, in the cells (or in the body fluids) but no necesarilly everywhereor in the same amount. For example, some receptors are present in the muscle cells but not in the nervous system and so on.
The histamine receptors can be found amongst other in the smooth muscle of the bronchi, gut and uterus, in the central nervous system and in the stomach.
These receptors are proteins, and proteins are very peculiar moleculles. They can be different in respect of the little, small pieces they are made but and the end, they perform the same function due to their final shape (to kept it easy). Also or maybe for this reason they are proteins which are a bit different from each other but that perform more or less the same function, for example histamine receptors, there is not only one unique histamine receptor in the universe. Different living being have different proteins as the proteins are given by the genetic code which is different in every living being, but even inside of the same body, there are histamine receptors which even if they interact with histamine, they are a bit different from each other. They are called receptor types (or even sub-types).
For the family of the histamine receptors only four receptor types are known, called H1, H2, H3 and H4.
This nomenclature is kind of common, some capital letters (H for histamine) and a number which usually denotes the other of discovery of the receptor.
Different receptor types of receptor are present (expressed) in different cells (tisues, parts of the body) and asociated to different metabolic effects (allergic response or secretion of gastric acid).
Histamine will, obviously interact (bind, anchor) with all these receptor types (and subtypes) and therefore histamine is an in-expecific moleculle (sometimes called substrate).
As every receptor type is expressed in different cells and regulates different metabolic effects, for the development of new drugs it is of primordial importance to create moleculles which are able to bind in a specific and selective way only one of the receptor types (or subtypes) so that for example, the allergic reaction can be blocked without disturbing the secretion of gastric acid.
Known Facts about the histamine receptor types are:
  • H1: to be found in the smooth muscle of the bronchi, wherein it regulates the contraction of the bronchi which leads to restriction of air flow in the lungs (if you have asthma, you know how it feels). Also the permeability of the capillary walls is regulated so that plasma constituents could flow into the extracellular spaces and produce an edema (basically the lungs are flodded with liquid and respiration becomes difficult). This receptor is also in the Central Nervous System wherein it is associated with drowsiness or somnolence. Drugs able to interact with this receptor are useful in the treatment of allergy and inflammation.
  • H2: plays a minor role in allergic inflammatory processes but in the stomach, parietal cells (the cells in the wall of the stomach) stimulation increases production and secretion of acid. Drugs able to interact with this receptor are useful in the treatment of ulcers.
  • H3: occurs in the brain, and it activation leads to a decrease in neurotransmiter release which promotes arousal, attention and improves learning (at least in animals). Allergic rhinitis is one condition in which drugs able to interact with this receptor may be useful.
  • H4: the more obscure, appears to be limited to cells of the hematopoietic (or hematogenesis, formation of blood) system and its stimulation results in a chemotactic response (movement or orientation of an organism or cell along a chemical concentration gradient either toward or away from the chemical stimulus, basically cell migration). The presence of this receptor on these cells suggests that this receptor plays a role in the inflammatory response.

Enough for today :)

Sunday, September 19, 2010

No one is left behind


Based in a true story, until yesterday unknown to me, this very decent and elegant (if you allow me) movie remembers me of the "old" war movies about WWII.
It does not portrait the life of the soldier as great and very masculine, nor as heroic unkillable killing machines, does not make too much of propaganda for the U.S. forces and has not a "happy ending".
The movie just relates the odyseey of a group of US soldiers trapped in the middle of hostile territory in the city of Mogadishu (Somalia) during a "failed" operation to arrests the main warlord at the time, Mohamed Farrah Aidi (wiki).
The movie is based on a book of the same title (wiki) and both seem to be a fair account of the disaster.

Shinies

No gold, no jewels, no funky glass, but Clone Troopers.
They (We) are the best troops of the Galaxy, if full trained.
They (We) have the best genetic potential thanks to our "father" Jango Fett, but without proper training they (we) are like an uncut diamond.
Today I watched the Episode 5 of the 1st Season of the new animated series The Clone Wars where a bunch of shinies (new, non completely trainer Clone Troopers) man a small outpost on the observation line of the Republic. The line is formed by a large number of such outpost with the mission to establish a perimeter of early warning for incoming Separatist attacks.
Not needing to say, a droid commando tries to seize the outpost to allow a Separatist fleet to approach Kamino unnoticed.
The Episode is simple (as all the episodes of this TV Series) but the wakening op the shinies is great. They discover what for a potential they have.
Also, as far as I know, this Episode mentions by the very fist time the existence of the 501st, the elite legion of the Empire, which started as an Elite Clone Trooper group.

Defend the Republic, join the Empire ;)

Saturday, September 18, 2010

Mexican Law


Just back from the cinema and still laughing.
This is movie is just crazy. The whole idea and set up is weird and funny.
I don't know what to tell you about without being a spoiler.
Just go to watch it, and be prepared for some gore, killing not machine, but Machete :D

Now, You know what I do for a living


Great movie.
True, Stallone looks old, but let's face it, he is old.

But, as far as I know this movie is the first and only one with Stallone, Schwarzeneger and Willis on it.
The scene they play together is just great.
I concede that Arnold only plays less than one minute in the movie, but, on the other hand he is retired from the movie business, maybe too busy being Governator (and being parodied by The Umbilical Brothers [Official Site]).

The plot is very linear ad without many surprises, but that is not the point, this movie is not Casablanca, but more like a burger in a MacDonalds, you know what you are getting for your money.
And in this case, what you get is a bunch of action movie guys beating up a whole army :D :D

Hope you enjoy it !

Thursday, September 2, 2010

Bad Evil Distillery

Last week we were in Scotland for a short holiday. The country is great, full of nice people and beautiful places (also the other way around ;D ).

The idea of the holidays was to spend a long weekend in Edinburgh (Military Tattoo included) and surroundings, therefore our time schedule was a bit tight.

Thursday was the visit to Castle Rock (wiki), an impressive construction and view point of the city. Friday was the free walking tour in Edinburgh (Official Site) and a comedy show (Pappy's All Business).

Until that point in time everything was smoothly according to the plan.

Saturday was a very compact day. The idea was to pick up a rental car in Edinburgh at 0800 and head for Loch Ness to be back in Edinburgh the same day late in the evening (well, night). In the way to Loch Ness we intended to visit Stirling, Callander, Glen Coe, Fort Williams and Fort Augustus (south end of Loch Ness) and back over Perth to the initial city.

Along the trip we wanted to visit the Ben Nevis Distillery (Official Site) which should be open until 1600. So we hurry up to be there with plenty of time to be able to visit the place, taste some whisky and buy some bottles. We were serious about buying as in our group there were two persons who actually love whisky and who actually planned their holiday's luggage letting some extra empty room for the bottles. According to the webpage of the distillery, the place should have been fantastic and the visit to the place should have been one of the nicest moments of the trip.

That was the Theory. Reality was a total disappointment.

We arrived there at 1500 (sharp) but the only lady there promptly informed us that even if it was one hour before closing time, it was not possible to visit the place anymore but that the shop and the visitor centre were, of course, still open.

According to the webpage:


"After your experience with Hector, a conducted tour of the production areas by a trained guide concludes with a complementary 'tasting'.

After your tour around our distillery why not relax with a refreshment or if you are hungry, try some of our delicious home cooking in our coffee shop and restaurant. It will be an unforgettable treat."




However, there was nothing there to drink or to eat. Even the tasting was impossible, because as apparently they do not have a "Pub licence", they are not entitled to serve you alcoholic drinks. I was not aware that you would be punish in the UK by offering alcohol for free inside of a building to an adult person. But, of course, if you were part of a group, then the tasting was included in the visit (?!)

Incidentally I must say that such a group happens to arrive at the same as us, therefore all the attention of the only lady there was focused on this group with total disregard to our small group (only six of us) and a poor couple which was waiting in front of the desk to buy some souvenirs or some bottles, what exactly I don't know.

Briefly said: If you are in Scotland, enjoy the country, but don't waste your time with this distillery. It is not worth of your time. There are more pleasant things to do in Scotland that to be disregarded by a mindless minion.

Obviously, our two whisky lovers were totally sunken by the "unforgettable experience!".

However, the day after we visit The Scotch Whisky Experience (Official Site) which was, by far, a better place.