celle membrane

09-11-16:// my first of my notes from semester one of med school! This one focuses on the cell membrane. This is a compilation of knowledge I’ve gained through lectures, textbooks, and other resources. I really want to try to build a resource for other med students to use when needed - if any of you notice any mistakes in anything I post, please let me know! c:

Hope you enjoy - I’m going to try to post a page like this each day, so stay tuned for more! 

Pharmacokinetics Overview

(Absorption and distribution of drugs)

The study of the time course of drugs and their metabolites in the body (what the body does to the drug) consisting of:

  • administration
  • absorption
  • distribution
  • metabolism
  • excretion

Administration

Enteral (passes through intestine)

  • oral (mouth)
  • buccal/sublingual (applied in cheek/under tongue)
  • Gastrosomy (surgical opening through the abdomen into the stomach)

Topical (applied directly)

  • Nasal
  • Rectal
  • Ophthalmic (eyes)

Parentral (injection)

  • Intravenous (into veins)
  • intramuscular (into muscles)
  • intradermal (within layers of skin)
  • subcutaneous (under the skin)

Drug molecules move around the body either through bulk flow (bloodstream, lymphatics or cerebrospinal fluid) or diffusion (molecule by molecule over short distances)

Absorption 

Passage of drug from its site of administration into plasma - important for all routes except intravenous injection.

Injection

  • IV = fastest route of administration
  • bolus injection = very high concentration of drug
  • rate limiting factors = diffusion through tissues and removal by local blood flow

Drugs need to pass through membranes (cell membranes, epithelial barriers, vascular endothelium, blood-brain barrier, placenta barrier etc) via

  • passive diffusion through lipids
  • carrier-mediated
  • passage through membrane pores/ion channels
  • pinocytosis (ingestion into a cell by the budding of small vesicles from the cell membrane)

Diffusion through lipid

  • non-polar molecules can dissolve freely in membrane lipids
  • the rate is determined by the permeability coefficient (P)(solubility in the membrane and diffusibility) and the concentration difference across the membrane

pH and Ionisation

  • Many drugs are weak acids or weak bases
  • exist in unionised or ionised forms
  • pH = balance between the two forms
  • ionised forms have low lipid solubility
  • uncharged however the drug is usually lipid soluble

ionisation affects:

  • rate of drug permeation through membranes
  • steady state distribution of drug molecules between aqueous compartments if pH difference exists between them

Therefore:

  • urinary acidification accelerates the excretion of weak bases and slows that of weak acids
  • alkalisation has opposite effect
  • increasing plasma pH causes weak acids to be extracted from CNS into plasma
  • Reducing plasma pH causes weakly acidic drugs to become concentrated in CNS, increasing neurotoxicity

Bioavailibility

  • Bioavailibility (F) indicates the fraction of an orally administered dose that reaches systemic circulation intact, taking into account both absorption and local metabolic degradation
  • determined by comparison between oral and IV absorption

affected by:

  • drug preparation
  • variation in enzyme activity of gut
  • gastric pH
  • intestinal motility

Volume of Distribution

Vd is defined as the volume of fluid required to contain the total amount, Q, of drug in the body at the same concentration as that present in the plasma, Cp

  • determined by relative strength of binding between drug and tissue compared with drug and plasma proteins
  • tight binding to tissue but not plasma –> drug appears to be dissolved in large volume –> large Vd (eg chloropromazine)
  • tight binding to plasma –> V can be very close to blood volume –> low Vd (eg warfarin)

The Golgi Apparatus is a membrane-bound organelle in the cell that receives proteins and lipids from the rough endoplasmic reticulum. It modifies some of them and sorts, concentrates and packs them into sealed droplets called vesicles. This organelle can be seen using an electron micrograph. 

The skin, neither moist nor dry, is a permeable membrane of cells dividing the summer landscape into pink and blue. Spring aches in the heart and stomach, the surfacing of women in moist soil and moonlight.
—  Christopher Dewdney, closing lines to “This is of two worlds …,” The New Oxford Book of Canadian Verse in English, chosen by Margaret Atwood (Oxford University Press, 1982)

04.01.2017

Today I studied :

Biology - recapped the cell structure of eukaryotic and prokaryotic cells and their organelles. Wrote some more notes on cell membranes.

Sociology - wrote some notes on research methods

Me hearing about the double bonds in unsaturated fats in the phospholipid bilayer that add the kinks that give the cell membrane its fluidity: brain, please don’t remember this by making it smutty
Me ten seconds later: all those kinks help get stuff up in you ( ͡° ͜ʖ ͡°)

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Listen to #528DNA - This music is encoded with 528 Hz Healing Frequencies By @4biddenknowledge AKA @coachbillycarson
#iTunes #CDBaby #GooglePlay #Amazon #Spotify #Tidal
Your #DNA is not set in stone. It can be transformed. According to #DrLeonardHorowitz, the #528Hz frequency has the ability to heal damaged DNA. At the time I am writing this, there is not enough scientific research available on the subject. What we know for sure is that Dr. Horowitz learned the theory that 528 Hz #frequency repairs damaged DNA from #LeeLorenzen, who was using the 528 Hertz frequency to create clustered water. Clustered water is broken down in small stable rings or clusters. Our DNA have membranes that allow water to flow through and clear impurities. Because clustered water is smaller than bound water, it flows more easily through cell membranes and is more efficient in removing those impurities. The larger, bound water does not flow easily through cell membranes, and therefore the impurities remain and can eventually result in illness. #RichardJSaykally from #UCBerkeley has explained that the structure of the water molecule gives it special properties and is essential for DNA’s function. Adequately hydrated DNA hold far greater energy potentials than dehydrated strands. Prof. Saykally and other genetics from the #UniversityOfCalifornia, Berkeley have proven that a slight reduction of energized water bathing genetic matrices causes DNA to fail energetically. #LeeLorenzen and other investigators discovered that six-sided, crystal-shaped, hexagonal clustered water molecules form the supportive #matrix of healthy DNA. He suggests that the depletion of this matrix is a fundamental process that negatively affects virtually every physiological function. Biochemist Steve Chemiski says the 6-sided clear clusters that support the DNA double helix #vibrate at a specific #resonant frequency – 528 cycles per second. @pantheoneliterecords
#4biddenknowledge

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Self-heating plants

Have you ever seen a plant growing up through the snow, and wonder how it can resist the cold so well? In some cases, like this eastern skunk cabbage (Symplocarpus foetidus), the plants actually melt the snow around them, using a trick very similar to the way warm-blooded animals stay warmer than the air around them.

The processes of life are a very deilcately balanced chain of chemical reactions, passing energy from one molecule to another to do work such as building other molecules and transferring substances across the cell and through membranes. Any difference between the amount of energy stored and the amount used to do work is released as heat. For the most part, cells seek to minimize the amount of “wasted” energy to avoid overheating.

One of the most common energy-transferring reactions uses the force of protons (H+) falling across the inner membrane of the mitochondria from an area of high proton concentration to lower concentration. Similar to the way that a generator uses falling water to generate electricity, an enzyme called ATP synthase uses the energy of these falling protons to make ATP from ADP. The ATP stores this energy in conveniently-sized packages to provide energy for wide array of cellular work.

If the protons are allowed to fall straight through the membrane, bypassing ATP synthase, the stored energy is “wasted”, turned entirely into heat. Certain cells in warm-blooded animals, such as brown fat cells, turn on this bypass on purpose, keeping body temperature warm even when the surroundings are cold. This bypass works by activating so-called uncoupling proteins, which provide a shortcut for the protons, uncoupling the process of cellular respiration from the manufacture of ATP.

Some plants that get a very early start in the spring have uncoupling proteins, too. By allowing their mitochondria to short-circuit the protons generated by oxidizing stored sugars, they can heat themselves a remarkable 15–35 °C (27–63 °F) above the temperature of the surrounding air. This melts the snow around them, and allows their enzymes to work more efficiently in the warmer conditions. By flowering earlier, they get almost exclusive access to the first round of pollinating insects, and can complete their lifecycle before the trees surrounding them leaf out and block most of the sunlight.


Reference: Wikipedia article for Eastern Skunk Cabbage

Image credit: Wikimedia user Seon7376, Creative Commons BY-SA 3.0

Dihydrogen Monoxide (DHMO) is a colorless and odorless chemical compound, also referred to by some as Dihydrogen Oxide, Hydrogen Hydroxide, Hydronium Hydroxide, or simply Hydric acid. Its basis is the highly reactive hydroxyl radical, a species shown to mutate DNA, denature proteins, disrupt cell membranes, and chemically alter critical neurotransmitters. The atomic components of DHMO are found in a number of caustic, explosive and poisonous compounds such as Sulfuric Acid, Nitroglycerine and Ethyl Alcohol.

Phroyd

ELI5:How come people can't be cryogenically frozen safely as the ice crystals destroy the cell membranes, but sex cells such as sperm are kept frozen for long periods of time yet remain functional?

I work in a lab where we freeze down cells all of the time. We freeze our cells in a medium that contains 5% DMSO, which among other things can be used as a cryoprotectant. However, DMSO is also toxic to cells at the concentrations necessary for cryoprotection. Consequently, when you freeze cells in DMSO, you add the DMSO medium at ice-cold temperatures and don’t allow the cells to warm up. When you later thaw the cells, you have to dilute out the DMSO as quickly as possible without causing osmotic shock, which can pop the cells. Such restrictions on freezing and thawing would basically be impossible to control at the level of a complete organism.

However, to contradict a lot of previous posts, individual cells can be recovered from freezing with high viability. When performed properly (and this varies quite a bit by cell type), you can expect >90% of cells to be alive following thaw.

The chemicals that allow cells to survive freezing are toxic to the body. Keeping the cells cold minimized the damage that this chemical does to the cells. With single cell solutions, adding the chemical at ice-cold temperatures and immediately diluting it out when you thaw the cells can keep 90% of the cells alive. There’s no way to do this with an intact body.

It’s also worth noting that this is probably not the only reason that this technique doesn’t scale to organisms.

Explain Like I`m Five: good questions, best answers.

youtube

What would it be like to watch a virus assemble?
CellVideoAbstracts posts “Assembly and Budding of a Virus from a Membrane Microdomain” from a recent article by Ruiz-Herrero and Hagan in Biophysical Journal. The video simulates how the shell of a virus, which is made of a protein called capsid, is enveloped by the host cell’s plasma membrane. As the virus packages its genetic material, it buds from the membrane so to infect the next cell.

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Tetrodotoxin

Tetrodotoxin, frequently abbreviated as TTX, is a potent neurotoxin. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several species that carry the toxin. Although tetrodotoxin was discovered in these fish and found in several other animals (e.g., blue-ringed octopus, rough-skinned newt, and Naticidae) it is actually produced by certain symbiotic bacteria, such as Pseudoalteromonas tetraodonis, certain species of Pseudomonas and Vibrio, as well as some others that reside within these animals.

Tetrodotoxin inhibits the firing of action potentials in nerves by binding to the voltage-gated sodium channels in nerve cell membranes and blocking the passage of sodium ions (responsible for the rising phase of an action potential) into the nerve cell.

TTX is extremely toxic. The Material Safety Data Sheet for TTX lists the oral median lethal dose (LD50) for mice as 334 μg per kg. For comparison, the oral LD50 of potassium cyanide for mice is 8.5 mg per kg, demonstrating that even orally, TTX is more poisonous than cyanide. TTX is even more dangerous if injected; the amount needed to reach a lethal dose by injection only 8 μg per kg in mice.

Cytodiérèse : télophase

Pendant la mitose, la cytodiérèse est le processus de division en deux de la cellule (cyto- : cellule / -diaeresis: séparation), qui s'étend entre l'anaphase et la télophase. Lors de l'anaphase, un anneau contractile composé d'actine et de myosine de type II se met en place sur le plan équatorial, et est ancré à la membrane par différentes protéines.

Puis lors de la télophase, cet anneau se contracte et comme il est solidaire avec la membrane celle-ci va s'invaginer, formant un sillon dit de division. Les microtubules polaires, qui relient les deux centrosomes et qui sont les derniers microtubules restant du fuseau mitotique, forment ce qu'on appelle alors les corps intermédiaires. Lorsqu'ils se dissocient, les deux cellules filles deviennent indépendantes.

Ces schémas ont été faits pour mes ED du Tutorat à partir des cours que j'ai retranscrit quand j'étais en première année de médecine. Ma seule source est le professeur de l'époque, et je peux avoir mal compris certaines choses, faire des approximations fausses, etc même si je fais de mon mieux. Croiser les sources permet d'avoir des informations plus fiables. N'hésitez pas à commenter pour discuter des sujets abordés ! Schémas et explications faits entre 2015 et 2016.