Friday 22 February 2013

pharmacology - Does a mydriatic drug neutralize the action of a miotic?

The iris has 2 sets of muscles:



  1. The circular muscle (Sphincter iris) - This causes iris constriction and is supplied by the parasympathetic system - Acetyl Choline muscarinic receptors

  2. The radial dilator muscle - This causes dilation of the iris and is supplied by the sympathetic system - The Adrenergic receptors (Alpha 1)

Theoretically speaking, there can be four sets of drugs:



  1. Alpha 1 adrenergic stimulators - will cause midriasis

  2. Alpha 1 adrenergic blockers/antagonists - will cause miosis

  3. Muscarinic blockers - will cause midriasis

  4. Muscarinic agonists/stimulators - will cause miosis

In practice,



  1. Midriatics:



    • Alpha 1 agonists: Phenylephrine

    • Muscarinic antagonists: Atropine, Homatropine, cyclopentolate, tropicamide


  2. Miotics (mainly used for Glaucoma):



    • Muscarinic agonists: Pilocarpine, carbachol, etc...

    • In practice alpha 1 antagonists are not usually used to effect miosis


enter image description here



There are two ways to achieve either midriasis:



  1. Stimulate the Adrenergic receptors

  2. Inhibit the Muscarinic receptors

Similarly miosis can also be achieved vice-versa.



The answer to your question is yes, when given the proper counter-acting agent, depending on the concentration of the agents and the mechanism of actions opposite effects are achieved. This is primarily because the drugs act on different sets of muscles. If a adrenergic stimulator - phenylephrine is instilled with a muscarinic stimulator - cyclopentolate, both sets of muscles will be acted upon and based on the concentration of the drugs, the decay rate and the efficacy, the iris diameter will either increase or decrease to variable degree. The point is that both the drugs will affect the final diameter of the iris (which is based on the autonomic state of the patient and the strength of drugs administered)



Now the special cases will be to administer a inhibitor of a receptor followed by an stimulator of the same receptor or vice-versa - In this scenario, the duration of action and the affinity of the given drugs to the receptor in question will play a decided role in determining the final action as both drugs act on the same muscle. If the inhibition is permanent or long-acting then inhibition of the muscle action is predominant. This may change if the stimulator has a very high affinity to the receptor - Higher affinity will result in tighter binding of stimulator and remove the chance for the inhibitor to work - i.e. increase the probability of the clearance of inhibitor. As you can see from above statement, if the clearance rate of inhibitor is slow (takes too long to metabolize), then the effect will ultimately be inhibitory effect. Similarly in case of poisonings where the stimulating effect is permanently achieved (Organo Phosphorous poisoning will cause permanent damage to acetylcholinestrase the enzyme responsible to remove acetyl choline) the reversal will depend on the affinity of the inhibitors (in this case, of acetyl choline) to the receptors (muscarinic).



Thus the question must be more specific to get a proper answer, as the effect is totally dependent on the drugs administered.

Sunday 17 February 2013

biochemistry - How to manufacture different sized micelles in nano -scale?

A key factor that determines the radii of a micelle is the critical micelle concentration. The other is the the hydrophobicity of the micelles which can be measured using the contact angle. A lipid nanoparticle has a minimum size on the order of 50 nm due to the surface tension of the lipid bilayer. However, micelles can be much smaller.



As for the creation of uniform nanoparticles, I am going to claim that what I say next can be in no way a reasonable answer to a HW problem. Why? Because the information is hidden in some obscure PLoS paper (Stapleton and Swartz) with 7 citations using IVC. Typically, micelles created for emulsion-PCR are created by vigorous mixing and followed by an extrusion step. However, this creates a polydisperse droplets. Alternatively, if you were to use a microfluidic device, then more monodispersed droplets can be formed. The control of droplet size can be achieved by varying the flow rates of the aqueous phase and the oil phase as well as changing the surfactant.



Micelles

Friday 15 February 2013

evolution - How did the first self replicating organism come into existence?

This is an extremely interesting and extremely fundamental question, indeed, and thus far, biologists have failed at coming up with a satisfying answer.



We know that all the parts are there, we just don't know how they were arranged, or which ones go where.



The question is, in essence, composed of three sub-questions:



  1. How did the fundamental building blocks of life come about?

  2. How did the first self-replicating molecules come about?

  3. How did cell membranes come about?

The answer generally takes the form of "On primordial Earth, a small selection of the billions of organic compounds generated when UV-light hits a mess of carbon dioxide, nitrogen and water where captured in a tide pool where concentration and foam led to random chance producing self-replicating molecules in proto-cells."



This answer, while almost certainly true, is also incredibly dissatisfying, because all it tells us is what deductive logic has already taught us, almost intuitively.



Incidentally, the fact that all of this happens with a million to one odds isn't a problem: The Earth is big, and the time frame for this happening is along the lines of hundreds of millions of years: Anything that might happen once per year by a million to one shot would likely happen hundreds of times in that timeframe.



In any case, when it comes to evolution, or Darwin's Theory of Evolution, or any other theory of evolution, this is all irrelevant.



Evolution is something that happens in any sufficiently complex (open) system, assuming it has the capacity to change at all.



It is most easily observed in living organisms, because they are at the right scale, and incredibly diverse, but it happens on all scales of the universe.



In fact, the easiest way to explain how life first originated, is just to keep counting backwards when you reach the Last Common Ancestor (of All Life on Earth), and propose models for how this proto-bacterium could be even simpler, until you're left with CO₂, N₂ and H₂O, and other simple molecules.



At that end of the spectrum it is well-understood that e.g. H₂O "evolves" from H₂ and O₂, because H₂O has a quality that makes it more "fit" than either of its components, chemical stability.



Furthermore, H2 "evolves" from free hydrogen by a similar mechanism, and free hydrogen "evolves" from protons and electrons, because it has the property of being electrically neutral, which is also a desirable property.



Of course, at the level of protons and electrons, things get a little muddy, and evolution kind of breaks down as a method for explaining how things come about.



Edit: For reference: Current Models of Abiogenesis on Wikipedia.

Thursday 14 February 2013

Is there any recent evidence for the aquatic ape theory of human evolution?

The Aquatic Ape theory has never gained wide acceptance. This is because it has never had strong evidential support.



The features supposedly supporting the hypothesis only do so under an extremely superficial analysis (e.g. the argument for bipedalism), frequently actually occur in other non-aquatic mammals (e.g. hairlessness in naked mole rats and rhinos, a descended larynx in red deer), show no sign of having arisen at similar times in the human evolutionary record (e.g. encephalisation evolved far later than bipedalism and bipedalism vastly predates hairlessness) and lack fossil evidence of having evolved near aquatic environments.

Monday 11 February 2013

dna sequencing - Alternate genetic codes in newly sequenced organisms

Variations of the standard genetic code are pretty rare, but as the cost of high-throughput genome sequencing continues to drop, there is a greater possibility of discovering additional exceptions. That being said, there is a clear emphasis in genome projects on nucleotide (genome and transcriptome) sequencing, with much less (if any) effort put into proteomics work (correct me if I'm wrong there).



Let's assume we're sequencing the genome of a new organism and we're focusing completely on genome and transcriptome sequencing--no proteomics. Let's also assume this organism has slight variations to the standard genetic code. Would it be possible to annotate this genome (for protein-coding genes) completely incorrectly since the gene prediction software does not take into account these variations, or would it be pretty obvious? What would you expect to see in this case?

Saturday 9 February 2013

Spatial resolutions in optical microscopy

I have read that different optical imaging techniques such as such as wide-field microscopy, confocal microscopy or STED microscopy can theoretically achieve a different spatial resolution.



However, I was only able to find information about the STED microscopy's spatial resolution (5.8 nm) on Wikipedia.



Does anybody know of any references or recommended reading (preferably free) where I can learn more about different optical microscopy methods and how the cope with the diffraction limit?

Friday 1 February 2013

natural selection - Why do only two sexes exist for animals?

To get a non-circular answer to why humans and other mammals have only two sexes, it's helpful to take a look at our evolutionary history. While mammals possess several adaptations to a terrestrial life cycle, including internal fertilization and gestation, which require substantial anatomic specialization between males and females, these are all secondary features that evolved long after our aquatic ancestors had acquired two distinct sexes.



Indeed, if we look at animals like fish, which reproduce via external fertilization, it's not at all obvious why they might not have more than two sexes. After all, for many aquatic animals, mating involves little more than the female and the male releasing their respective gametes into the water, where they meet and fuse to a form new zygote, which can then divide and grow into a new adult. Seen that way, there seems to be no reason why there could not be more than two "mating types", as in many fungi, such that gametes of any two distinct types could fuse into zygote.



The answer lies in the fact that the male and female gametes aren't actually that similar: the female gametes, or eggs, are typically large cells that contain all the nutrients necessary for the new zygote to develop into a viable individual, whereas the male gametes, or sperm, are tiny and produced in huge numbers. This asymmetry is known as anisogamy, and modeling its origin has been an important topic in the theoretical study of evolution.



Without going into details on the evolution of anisogamy, once it exists, it clearly forces the mating types to also split into two groups: there's no advantage in two microgametes (sperm) fusing, since the resulting zygote would lack the nutrients it needs to be viable, whereas the fusion of two macrogametes (eggs) would simply be inefficient — eggs, being large, are comparatively rare and expensive, and wasting two of them to produce only one offspring would be suboptimal even if the resulting zygote was viable. Nor is there really room in such a scheme for gametes of intermediate size: they'd be too small to fuse into a viable zygote with sperm, but too large to be produced in sufficient amounts to be effective in fertilizing eggs.



Of course, there's nothing that would stop a single adult from producing both micro- and macrogametes, but such an adult would not really be a third sex — it would just be male and female at the same time, a mating strategy known as (simultaneous) hermaphroditism, which indeed occurs relatively often in nature.



So, if pretty much all animals are anisogamous, why do fungi remain isogamous (and often have multiple mating types), then? Well, one explanation is that the main drivers for the evolution of anisogamy — sperm competition and transportation risk — don't really apply to fungi, which mate when two sessile haploid mycelia grow and come into contact with each other. Since the gametes are not motile, there's no advantage for either/any sex to produce more of them (at the cost of smaller size) in order to increase the chance of successful mating. Thus, isogamous mating works fine for the lifestyle of fungi, and having multiple mating types is then a useful adaptation to make successful mating between neighboring mycelia more likely.