| 00:11 | I. Mhm. Yeah. thank you for right. Ok. |
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| 00:47 | . Mm. The best thing in Oh. Oh, ok. |
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| 01:19 | I am definitely. OK folks. welcome, sorry for the delay. |
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| 01:28 | Anyway, I wrote that reminder email long ago and I completely forgot to |
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| 01:33 | exam three in there. So remember starting at tomorrow uh Saturday, so |
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| 01:39 | your daytime reservation on that. Um uh we are as you know, |
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| 01:48 | of ahead of the game here. we're uh gonna finish up um a |
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| 01:56 | , just a tiny bit of 18 left on, on vaccines and then |
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| 02:00 | chapter 20 which is not that long , but we'll get through most of |
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| 02:04 | today and have a little left over next Tuesday. So next Tuesday we're |
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| 02:10 | finish 20 then start diseases. And um uh the uh disease. So |
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| 02:20 | you look ahead to that um you , take a look at it |
|
| 02:25 | just in terms of I keep saying memorize everything when you study that actually |
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| 02:30 | be diseases. Part is a lot that I I would say, |
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| 02:36 | and there's a way to, so one you're seeing 25 to 2026 5 |
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| 02:42 | . Oh my God. No, just selected diseases from those five |
|
| 02:47 | So, uh by no means any those chapters in their entirety. |
|
| 02:51 | uh so there's a, I have list um of the pathogens. Uh |
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| 02:56 | of what to know, OK, , about this, about them. |
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| 03:01 | it's great. You know, the way to me is like to make |
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| 03:03 | table. OK? Here's a, a column of pathogen, here's the |
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| 03:08 | it causes, here are some things it features whatever. So, uh |
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| 03:13 | you look in the, in the , hidden notes for that, you'll |
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| 03:16 | an example of a table kind of to construct it. That may be |
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| 03:20 | best way to do that. Um , uh anyway, so that's, |
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| 03:25 | what we're gonna finish up this semester and very likely the last day, |
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| 03:29 | a little bit of that left to . So I don't see the last |
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| 03:33 | being a full day. Um Who where we finish on on that Tuesday |
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| 03:38 | then. But anyway, that's, , that's the plan. So, |
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| 03:43 | let's see. So weekly quiz. although this, the quiz this week |
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| 03:50 | an extra day inadvertently, uh I ahead and just added an extra day |
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| 03:55 | that one too. So it's not until Tuesday uh simply because you got |
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| 03:59 | exam. And so, you just take a, you know, |
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| 04:03 | gives you Monday and Tuesday to kind think about that because obviously you're not |
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| 04:08 | about the quiz right now. You're exam three mode. So, |
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| 04:11 | so it will be due on, says Monday it will be due on |
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| 04:14 | . Ok. Um, and then think, uh, there isn't, |
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| 04:22 | , I don't think there's any smart due until not this Monday, but |
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| 04:26 | Monday the 27th I think is when smart work, the first ones are |
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| 04:30 | for this last unit. So, anyway, uh let's see, I |
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| 04:35 | that's that get so um all So let's, so we talk, |
|
| 04:43 | been talking about um vaccines. So , it's, it's an extension of |
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| 04:49 | chapter um uh 17 on um the response, right? Adaptive immune response |
|
| 04:56 | obviously vaccines are uh are work because the primary secondary immune response, |
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| 05:04 | Um And uh your body responds to by forming antibodies. Uh The best |
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| 05:11 | we try to construct, stimulate you know, your B cells and |
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| 05:16 | cells and get all that going. But sometimes you are, you have |
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| 05:20 | deal with the type of agent, , you're making the vaccine for. |
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| 05:26 | like those um like meningitis pneumonia, are ones where the capsule is, |
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| 05:33 | the antigen that we're targeting, And so capsules are are sugar molecules |
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| 05:38 | aren't the greatest antigen in terms of a mirror response. So we um |
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| 05:43 | try to boost that up by adding protein to it. That's what was |
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| 05:47 | uh vaccine. So, you not in all cases, can it |
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| 05:51 | a protein antigen that just depends on pathogen and, and what it's and |
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| 05:56 | your body responds to on it. , um the uh so uh the |
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| 06:04 | couple of things here have to do production and you know, not getting |
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| 06:08 | details by any means on this But, but um certainly production of |
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| 06:14 | has has greatly developed and it used be most vaccines. We just take |
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| 06:19 | organism. You, you had the attenuated type where you killed it and |
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| 06:24 | it. Those used to be the ways to do it. But now |
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| 06:27 | course, very common in DNA technology up a whole other ways to do |
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| 06:31 | things. So you know, your vaccines of various forms can now be |
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| 06:36 | constructed. Uh The latest, latest of latest technology now is the MRN |
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| 06:42 | vaccines like we saw with COVID. so, you know, one approach |
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| 06:48 | obviously um the vaccine production is finding , constructing vaccines is something that uh |
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| 06:57 | for existing ones, right, the you get charged for already don't have |
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| 07:03 | not last forever in terms of being giving the most robust immune |
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| 07:08 | So you you're constantly also um not vaccines for newer diseases, but kind |
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| 07:15 | playing with the ones we already have for to make them better So, |
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| 07:20 | and so you can, this is showing you kind of a nice |
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| 07:26 | which you call this meningitis obviously. you know, all the different engines |
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| 07:31 | basically all the the uh it's entire , right, which is gonna be |
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| 07:36 | of mostly protein coding genes. And of these are gonna be uh code |
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| 07:41 | proteins that are on the periphery. know, those are typically the ones |
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| 07:45 | are, that will give the immune . So you can kind of get |
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| 07:48 | profile of, of classifying these different of genes and the proteins they make |
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| 07:55 | where they're at in and on the and the candidates for something that might |
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| 07:59 | a vaccine, of course, are be things that are on the |
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| 08:02 | right? Like a uh uh um capsule or what have you, |
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| 08:07 | And so you can then take uh is all done. A lot of |
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| 08:11 | is done using computers and database information so forth. Uh But you can |
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| 08:17 | pick out, you know, what be and it's for a good energy |
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| 08:22 | give an immune response because it's sitting the surface somewhere. OK? If |
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| 08:27 | a febrile uh protein or pili protein what have you. And then you |
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| 08:34 | say, OK, let's express those . OK? And then let's test |
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| 08:39 | , right. Put it here all animal models of some sort. |
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| 08:42 | put it into the mouse. Is producing antibodies? Can we then take |
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| 08:46 | antibodies and see, well, how they work against the pathogen, |
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| 08:50 | And so these are all kind of screening types of things you do to |
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| 08:55 | out. Ok. Well, this particular one is a good |
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| 08:58 | This one doesn't this one? so, so you can evaluate, |
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| 09:02 | it's a way to look at it kind of in, in the, |
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| 09:06 | the whole organism approach, right? seeing what might be the best antigens |
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| 09:11 | the next vaccine we make uh against . OK? Um So that this |
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| 09:16 | stuff going on all the time to to keep up with because obviously the |
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| 09:21 | aren't sitting there doing nothing, they're , they're changing, right? So |
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| 09:25 | have to uh make sure we stay of it. Uh Other things we |
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| 09:30 | to do um the, the, delivery mode of the vaccine because people |
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| 09:34 | needles, right? They wanna get shot, right? So you try |
|
| 09:38 | come up with um uh things like uh a pill perhaps or a patch |
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| 09:44 | uh uh drops. OK. What you um anything other than a |
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| 09:49 | But can always, it doesn't always . We try to do that uh |
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| 09:54 | combination vaccines. That's that um lessens number of shots you have to give |
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| 09:59 | shot, but they get, you , 33 vaccines in one rather than |
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| 10:03 | three separate shots. So that's what de tap uh vac uh vaccine is |
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| 10:07 | of those diphtheria tetanus pertussis is a three in one combination. Um |
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| 10:13 | we talked about adjument. I put in the same category as uh the |
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| 10:19 | vaccine, adding a molecule to it make it more uh immune responsive. |
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| 10:25 | uh so all these things are are to being worked on to improve. |
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| 10:29 | So of course, the other thing this is is getting a vaccine, |
|
| 10:35 | ? One thing is to make them , provide them, but then get |
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| 10:38 | to uh get people to get right? Because there has been |
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| 10:42 | I'll come back to that. There been fears here and there about, |
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| 10:47 | , they're not safe. Ok. happen. Yes, I mean, |
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| 10:52 | , I mean, there's no biological or otherwise that will be 100% |
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| 10:59 | know, right, all the But they do a lot and lots |
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| 11:02 | lots of testing with these and you know, the COVID was kind |
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| 11:07 | vaccine was kind of rushed, But there wasn't um a, a |
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| 11:13 | deaths attributed to people just from just the vaccine. Ok. So in |
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| 11:18 | , they are safe, right? you shouldn't necessarily have that fear. |
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| 11:23 | ok to ask right about. this, it's ok to question |
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| 11:27 | Of course, uh when you talk your doctor about it, but um |
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| 11:31 | should be able to alleviate your uh , right. Um And so, |
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| 11:37 | in fact, a lot of the effects that do happen come in the |
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| 11:42 | of the manufacturing side. So often viruses, you have to grow them |
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| 11:47 | in order to obtain the antigen. and you often grow them like say |
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| 11:52 | in chicken embryos, right? So need other cells to grow in. |
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| 11:55 | a chicken embryo is one that you used for that. And it could |
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| 12:01 | that products in the egg like proteins things can be things that people may |
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| 12:06 | to in the vaccine are not necessarily the antigens themselves. OK. So |
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| 12:11 | try to do lots of. So contain um you know, lots of |
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| 12:15 | right to minimize these kinds of Uh uh and and add, add |
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| 12:22 | that kind of help with that stabilize kind of things. So, but |
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| 12:26 | know, you can, you can some reaction to it but all the |
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| 12:31 | they do on these things beforehand, in, you know, it is |
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| 12:36 | uh to, to see that it a safe product. And so um |
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| 12:42 | because historically, it's been shown that with various uh immunization campaigns, you |
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| 12:52 | , whether it was polio in the , um Diphtheria, this had been |
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| 12:55 | the thirties in the thirties. Diphtheria the one of the main killers of |
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| 13:01 | . OK. Until when the diphtheria was developed, see how dramatically within |
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| 13:08 | 5 to 10 year span, the dropped as people, people got |
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| 13:12 | So, uh, you can see graphs for other diseases, uh, |
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| 13:17 | which, um, mumps and measles , et cetera. And so |
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| 13:22 | it's certainly proven effective. And um, again, back to that |
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| 13:26 | immunity. Right, you have to , uh, most of the people |
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| 13:30 | , um, 70% at least depending the disease to help, help those |
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| 13:35 | don't get vaccinated and, and there always be that and that's, you |
|
| 13:39 | , I'm not going to judge people they don't want have a vaccine. |
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| 13:42 | , you know, if it's, could be for religious reasons, it |
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| 13:44 | be for maybe they, their immune can't handle it and that's obviously |
|
| 13:50 | right. So, um but when an irrational fear, you kind of |
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| 13:56 | to walk them through it. But I think uh it's, |
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| 14:00 | it is a good thing. Um The uh any questions about |
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| 14:10 | we're kind of flip here to the one which is, oh, let |
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| 14:14 | just mention this real quick and I do this, don't, don't memorize |
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| 14:18 | thing, obviously. Uh this is uh speaking of how viruses viruses in |
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| 14:24 | case, viruses but applies to other as well. But this is the |
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| 14:28 | virus and these are all the variants , of, of the COVID virus |
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| 14:33 | the last three years. Um So had like the alpha alpha beta, |
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| 14:40 | delta omicron is the one uh certainly heard. And that's the, that's |
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| 14:46 | that's the current one. and it's a different variation. So the current |
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| 14:51 | , um it was uh so with is with these variants, that's the |
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| 14:59 | vaccines to those uh the, the A variant that was the prior vaccine |
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| 15:06 | last year. Now, that appears be the predominant strain and all these |
|
| 15:10 | , these numbers here, right. refer to that, that one particular |
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| 15:15 | protein we talked about earlier, how vaccine was constructed based on the the |
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| 15:20 | that coded for that spike protein. so it just represents all the variations |
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| 15:25 | that same spike protein, right? it's it was amino acid sequence. |
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| 15:29 | it changes and as it evolves and these different variants. And so these |
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| 15:36 | here, BBMBOC um bo I, are all are all kind of uh |
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| 15:46 | of kind of the uh how seriously being taken, so to speak. |
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| 15:52 | I think um a VOM is OK? We're aware of it and |
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| 15:56 | just kind of monitoring, it's not doing anything, you know that harmful |
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| 16:00 | much. But more of the other are kind of kind of about the |
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| 16:05 | of of seriousness, so to the transmissibility. OK. Anyway, |
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| 16:11 | the the the, so this is to show you that you keep |
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| 16:15 | right? So like a flu it's different every year because the virus |
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| 16:19 | other microbe is evolving as well. we have to keep up with |
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| 16:24 | Um So OK, chapter 20 kind basically an extension of vaccination and we're |
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| 16:32 | talking about antimicrobial agents here. um so we'll go through some of |
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| 16:38 | basic terms uh involved with this. so basically looking at um antibiotics |
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| 16:45 | and other drugs. And so let's at this question here. And |
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| 16:55 | selectivity is a very important feature of of these antimicrobials. So this adds |
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| 17:02 | most selective micro criminal activity would be by a drug that which one of |
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| 17:11 | would be sart most selective? Um . And, and OK. Count |
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| 17:50 | from three here. OK. Uh Yes. So that would be |
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| 18:05 | most selective, right? Because uh of obviously all cells have protein synthesis |
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| 18:11 | on has a membrane cle acids but everything has a cell wall. |
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| 18:18 | So the this um this idea of toxic, that's basically the hallmark of |
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| 18:26 | chemotherapy, right? Um Kill, the pathogen, don't kill the person's |
|
| 18:34 | you're trying to cure. OK. you always try to find agents |
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| 18:39 | that have that are selective. So course, bacteria being prokaryotes, different |
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| 18:45 | kots, obviously, there's a number targets there that only they have |
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| 18:50 | that we don't. And so uh even in some of the things that |
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| 18:54 | more that we overlap with them like protein synthesis, you know, they |
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| 19:02 | have ribosomes, of course, but , there's, they're gonna be a |
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| 19:04 | bit different in structure composition than So those are still valid targets. |
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| 19:11 | . Um And the components of DNA . So some of the enzymes there |
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| 19:15 | exactly the same. So you can some selectivity there, but certainly a |
|
| 19:19 | wall, right. So we don't pep glycan. So that's, you |
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| 19:22 | , that's, that's open for any of targets there. OK. That |
|
| 19:26 | can be sure it won't affect OK. Our ourselves. So, |
|
| 19:30 | , let's um uh probably the one of the main things in terms |
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| 19:35 | antimicrobials and finding new ones is to to that as best you can. |
|
| 19:40 | And so in terms of the, uh activity of these antibiotics, um |
|
| 19:46 | I'm sure, you know, we'll different um targets, right? So |
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| 19:51 | uh a narrow spectrum antibiotic might be that selective for gram negatives. |
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| 19:56 | Versus gram positives, something like It's gonna be more effective on the |
|
| 20:01 | positive types. And so other drugs be more uh broader spectrum uh that |
|
| 20:08 | target both gram negatives, gram OK. Uh The um so remember |
|
| 20:14 | the gram negative gram positive difference, ? That outer membrane of a gram |
|
| 20:18 | can be somewhat resistant to certain So it's a matter of finding types |
|
| 20:24 | can, can get through that outer that and um the uh super |
|
| 20:33 | So what this is is, let's you uh you have take, you're |
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| 20:42 | antibiotics for an infection, OK. uh that will kind of upset your |
|
| 20:50 | microbiome. OK. So in that that can then take off the the |
|
| 20:59 | of types that are in your Now that used to be held in |
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| 21:04 | by competition from those other members of microbiome. Now it goes down and |
|
| 21:09 | begin to proliferate. OK. Two the more common examples of that, |
|
| 21:14 | what they call a super infection. other one now takes over as your |
|
| 21:19 | is kind of has been affected you know, an antibiotics. And |
|
| 21:23 | this this other group takes, grows in its place. Ok. |
|
| 21:27 | , Clostridium DeFeo is one of You have it, many, many |
|
| 21:31 | us have it in our gut, it's, it's held in check by |
|
| 21:35 | normal microbiome there. And when they it, it's very typical in elderly |
|
| 21:42 | to get this and uh especially those are hospitalized with some other kind of |
|
| 21:47 | , whether it's a heart condition or and they will uh maybe give an |
|
| 21:52 | for some kind of um you superficial infection and then that disrupts their |
|
| 22:00 | microbiome. And that clostridium begins to in numbers that super infection and that |
|
| 22:06 | lead to serious um diarrheal disease and that can be fatal. Um A |
|
| 22:13 | infection like can candida causes a yeast . And so uh a a if |
|
| 22:19 | is on antibiotics for some other then that microbiome also, then fungi |
|
| 22:24 | aren't susceptible to antibiotics. And so may then begin to grow overgrowth causing |
|
| 22:29 | super infection. And so it's not lot of things do that. But |
|
| 22:33 | are kind of the two main examples what the super infection is, which |
|
| 22:37 | basically your antibiotics, your normal microbiota kind of affected by that kind of |
|
| 22:45 | by that. And then, then for the potential for others in there |
|
| 22:48 | kind of take over and grow. can be be uh harmful like a |
|
| 22:56 | a yeast infection or post the feile . Then there's a few other examples |
|
| 23:00 | that. OK. Um So uh , goes the importance of your microbiota |
|
| 23:08 | , you know, really keeping you in many cases, right? So |
|
| 23:12 | you do upset that balance, it's to kind of restore that as best |
|
| 23:15 | can. OK? Um Now, this we've talked about before in the |
|
| 23:23 | of um oh I think Checker I believe. But uh anyway, |
|
| 23:28 | actions of course, are, you , pretty basic, you're gonna kill |
|
| 23:31 | or you're gonna inhibit their growth, ? Bactericidal bacterial static. OK. |
|
| 23:36 | you can add in here uh bacterial because they both kill, OK. |
|
| 23:42 | uh in any case, you're gonna see uh growth declining, actively killing |
|
| 23:48 | , right? Viable numbers going down plato or just inhibiting growth. |
|
| 23:54 | So you might go, well, it? Why, why would I |
|
| 23:58 | have a bacteriostatic, an antibiotic? bacteriostatic, it's not killing anything. |
|
| 24:05 | would I want that? OK. Any thoughts like could be a bacterial |
|
| 24:11 | , you're gonna run and go. . Give me the bacterial cy |
|
| 24:17 | What advantage would it be back to stacking? That's it, it slows |
|
| 24:25 | down, right? So that's remember talked about um time as an |
|
| 24:33 | time buying time, right? So but you're a static agent can be |
|
| 24:40 | way to help you buy time. It could be an agent that maybe |
|
| 24:45 | live as a gram negative, The gram negative and the endotoxin |
|
| 24:49 | right? That gets killed then releases material. Well, that might be |
|
| 24:54 | good choice. A veter agent against gram negative infection possibly, right? |
|
| 25:00 | if it's become maybe in the blood um septicemic. OK? Uh Then |
|
| 25:07 | might be a good choice because then inhibit their growth, allow time for |
|
| 25:11 | immune system to catch up and help care of it, right? Rather |
|
| 25:15 | giving a bacterial Cyle agent in that , that can blow up the cells |
|
| 25:19 | that material causing a worse effect, ? So there are there are there |
|
| 25:23 | instances times when it's affected to use like that or I use it in |
|
| 25:29 | , you can use them in combination well. We'll talk about that. |
|
| 25:33 | one drug has this effect, another that put them together, they work |
|
| 25:37 | better. So there's examples of that . OK. Um, ok. |
|
| 25:44 | the uh action of antimicrobial. So you might think they're going to be |
|
| 25:49 | targets uh in the cell that disrupt protein synthesis in some way, either |
|
| 25:57 | and, or translation. Um, wall cell wall disruption. That's a |
|
| 26:02 | one. There's lots of antibiotics that that. Anything that pretty much ends |
|
| 26:08 | , uh, Illin, which are number of those works on it. |
|
| 26:13 | so do some of these others. . Uh Because there's a lot |
|
| 26:16 | there's a lot of parts uh enzymes in the bacteria making a cell |
|
| 26:21 | So it means there's lots of different there. OK. So you have |
|
| 26:25 | of antibiotics to those different ones. uh So it's putting synthesis that's typically |
|
| 26:31 | , affecting the ribosome. That's what antibotics interfere with uh the A |
|
| 26:37 | Uh Certainly for um there's parts of process that are um unique to the |
|
| 26:45 | . And so um the the uncoiling of it, proteins that do that |
|
| 26:51 | even uh some that bring about So those are typically targets as well |
|
| 26:57 | interfering with metabolic pathways. OK. see an example of that. There's |
|
| 27:01 | one. So uh the um um was the other one? A plasma |
|
| 27:08 | ? Right. So we can uh different things, the plasma membrane 11 |
|
| 27:13 | is to kind of have these uh that kind of stick themselves in the |
|
| 27:19 | like a, like a channel like tunnel and that causes leakage of the |
|
| 27:23 | . So there's drugs that can do . So, you know, um |
|
| 27:28 | broad spectrum of many different types of against the cell. Ok. Um |
|
| 27:35 | certainly inhibiting sool symptom is a big because of the uniqueness of that pep |
|
| 27:40 | hand. Uh so penicillin and many drugs, ampicillin, amoxicillin are all |
|
| 27:45 | that same boat um in a plasma . So you could do it through |
|
| 27:53 | probably peptide in the back. Those the ones that are like the little |
|
| 27:56 | , like just sticking a straw in and the contents leak out, |
|
| 28:00 | manipulate the ions. OK. So you do that, then you can |
|
| 28:05 | a uh osmotic effect, right? can come out of the cell and |
|
| 28:11 | a shrinkage and kill the cell um ines. So again, yes, |
|
| 28:18 | have ribosomes but ours are a little , right? And uh so they |
|
| 28:22 | be selective in just targeting uh the and not your cells. OK. |
|
| 28:29 | Streptomycin is one of those. And , ribosome has different components. You |
|
| 28:34 | have antibiotics for, for towards the components here. Um Tracy. So |
|
| 28:40 | attachment between, so the trn A in that tetra cycline interferes with |
|
| 28:46 | So different aspects of the process can counteracted by different antibiotics. OK? |
|
| 28:53 | you, you, you don't need memorize the table of antibiotics. I'm |
|
| 28:58 | gonna ask you what does tetracycline OK. So you don't need to |
|
| 29:01 | all that stuff. OK. More of what are the targets, |
|
| 29:05 | Protein synthesis. That's a membrane. happens there? Not specifics in terms |
|
| 29:12 | antibiotic and what it acts to which um all right, the um the |
|
| 29:20 | assets. So if you were in and you had that one media called |
|
| 29:27 | the Columbia Blood Order, it had , had the abbreviation CN A. |
|
| 29:34 | the end was for that now, acid. So it appears with |
|
| 29:39 | I mean DNA synthesis. Um And uh obviously, in doing so the |
|
| 29:44 | can tr genome is certainly not gonna able to reproduce um interfering with metabolic |
|
| 29:52 | . OK. So this is the to make nucleotides for DNA RN |
|
| 30:01 | OK? And the the sulfur which is kind of AAA generic name |
|
| 30:09 | a number of these that have a effect. This one's called sulfur metox |
|
| 30:15 | . These interfere. So these are one, the path me pathways are |
|
| 30:20 | out by enzymes. OK. So step is gonna be a different |
|
| 30:24 | And so this um drug uh shown uh has a has a very similar |
|
| 30:32 | to the actual molecule that's used to this this product. And so you |
|
| 30:38 | see in purple how similar it And so it interferes with the |
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| 30:43 | it competes with the uh with pab for the enzyme site and then you |
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| 30:49 | , it interferes with the production of , of the product here. The |
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| 30:52 | hydro folic acid. Similarly, uh one trimethoprim interferes with this step. |
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| 30:59 | enzyme carrying out this reaction. uh in doing so the cell |
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| 31:03 | can't make its nucleotide to replicate. . And so, um and so |
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| 31:09 | very common to uh interfere with enzyme , having a molecule very similar in |
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| 31:16 | structure. Like you see here, or green, very similar in terms |
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| 31:22 | structure. That's what the enzyme looks is, does it have the same |
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| 31:27 | ? If it does, it it can be fooled if you have |
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| 31:30 | similar molecule in time? Um Let's look at this question. And |
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| 31:38 | um this is about anti viral You guys remember um what? |
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| 31:46 | antibiotics don't work against viruses? So all the following are modes of |
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| 31:53 | of antiviral drugs, except which Um OK. Yeah. Yeah. |
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| 33:04 | you can have certainly the un coding is a, is a virus. |
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| 33:08 | a virus thing. That's a viral . So, uh there's certainly antiviral |
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| 33:13 | to that. Um DNA DNA Um They, many of them have |
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| 33:21 | own DNA ply that they use. they can be susceptible to that as |
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| 33:25 | as RN A synthesis. That was thing called RDRP. All right, |
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| 33:30 | , that enzyme. So, um protein synthesis, no, it's pretty |
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| 33:34 | for that. It's using all of host um components for that. So |
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| 33:40 | would not be a good target. . Um But certainly BC and D |
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| 33:47 | not, not, not for all , but for some, uh certainly |
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| 33:52 | they can be affected by a drug DNA sense of some RN A, |
|
| 33:56 | certainly on coding as well. Um . So, uh all right. |
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| 34:07 | entry and fusion in. So, , this goes to the remembering the |
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| 34:12 | uh the first part of the viral cycle, right? You have recognition |
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| 34:17 | to the host, but then you to do the get into the |
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| 34:20 | right. And so um uh those spiky proteins on the viral surface, |
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| 34:27 | of those are involved in in um and getting into the cell. |
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| 34:33 | And you can have drugs that block entry uh on coding the genome and |
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| 34:40 | nucleic acid inhibitors. So, preventing encoding process, right? Um that's |
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| 34:46 | the genome released. So you can of block that um uh inhibiting brown |
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| 34:52 | to the host chromosome. OK. typically viral enzymes involved in that you |
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| 34:57 | counteract with different types of drugs. a very common one is this. |
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| 35:03 | a nucleo side, it is basically nucleotide minus the phosphate, right? |
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| 35:10 | so you can have molecules that look this and that will interfere with the |
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| 35:14 | of the virus to um synthesize RN or DNA acyclovir is a very common |
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| 35:22 | that does that. OK. So is um the actual drug acyclovir very |
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| 35:30 | to uh the the oxy guanine, , especially in the purple, |
|
| 35:36 | Just different here. And so um how it works is to. So |
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| 35:44 | the normal scenario. So your cells take that nucleotide, take this enzyme |
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| 35:51 | then basically add, add the phosphates it. Oops. OK. And |
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| 35:57 | we go from Umano nucleic side to TP here, adding three phosphates to |
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| 36:07 | . OK. And that's what normally used to make to synthesize DNA, |
|
| 36:12 | course, as well as a uh all four of them. So |
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| 36:18 | the virus, the virus affect there is a change to the enzyme |
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| 36:25 | , that uh carries out this And so a cycle of your interferes |
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| 36:31 | it can't add on the phosphate OK. So it gets stuck right |
|
| 36:36 | . And so you don't get the looking nucleotide and it can't, it |
|
| 36:43 | synthesize DNA. And so uh so a way to stop the infection. |
|
| 36:49 | . Um It's, it's proven relatively . OK. For certain uh |
|
| 36:55 | I think um uh herpes is one type that this is used against uh |
|
| 37:02 | other DNA viruses. Um The, here an exit inhibitor, an example |
|
| 37:12 | this is Tamiflu and over the over counter medication. So uh against the |
|
| 37:22 | . So the flu virus has uh can have some effectiveness against it. |
|
| 37:29 | so this, this neuro Mease is it's a one of those viral |
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| 37:34 | viral proteins on the surface of the virus and when it exits it, |
|
| 37:40 | has to clip itself off the cell then be free right to infect other |
|
| 37:46 | . And if it's, and this apparently inhibits it from doing that, |
|
| 37:50 | it kind of sticks to the cell it, and it cannot go off |
|
| 37:54 | infect other cells. Ok. And , um, has any, has |
|
| 37:59 | taken Tamiflu? Did, did you that, did anything? Ok. |
|
| 38:09 | else at town flu? No. you, did you think it, |
|
| 38:13 | , it helped? Like it maybe you were sick for a fewer |
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| 38:19 | of days, maybe, or Ok. Uh, that's kind of |
|
| 38:23 | I read it. What it it can maybe re reduce your period |
|
| 38:27 | illness by a couple of days or . Ok. But, uh, |
|
| 38:30 | that has a lot to do uh, timing. I believe the |
|
| 38:33 | you take it after you think you've exposed that tends to be more effective |
|
| 38:39 | if you wait too long. It was kind of about the timing |
|
| 38:43 | it. Um, uh, I think I can kind of see |
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| 38:47 | because if the virus, you've just infected infect your cells and then now |
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| 38:52 | begin to come out. Right. that's the point where you really have |
|
| 38:56 | have the Tamiflu there to prevent them coming off the cell and affect |
|
| 39:00 | So you wait too long. There's too many, too many viruses that |
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| 39:04 | out there affecting other cells and you becomes a numbers game. You |
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| 39:09 | uh, you don't have enough dosage keep up with it. Ok. |
|
| 39:12 | , but if you do time it , it can relieve symptoms by a |
|
| 39:17 | days. Um, interference. We're about this before. Um They, |
|
| 39:26 | uh this Interferon itself was used to , was tried to be mass produced |
|
| 39:32 | sold as a drug. It didn't very well. Um because of toxicity |
|
| 39:36 | and other things. But they, , you can, they do have |
|
| 39:40 | drug that actually uh is not but it, it, you take |
|
| 39:45 | and it promotes interferon production in your . And so, uh I'm not |
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| 39:51 | how effective that's been. But uh know you can, if you have |
|
| 39:54 | severe viral infection and you get they can give you shots of Interferon |
|
| 40:00 | that proves effective. Ok. Remember the Interferon um uh will, will |
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| 40:07 | in uninfected cells, it kind of protect when the virus drives to |
|
| 40:11 | It basically um destroys the viral genome it comes in. Um HIV A |
|
| 40:18 | DS. So certainly the, that is that enzyme, this is the |
|
| 40:23 | that works against that reverse transcriptase, ? That certainly is AAA, you |
|
| 40:29 | find this in the virus, OK. And so ac T kind |
|
| 40:33 | interferes with its ability to, to the RN A into DNA. And |
|
| 40:39 | , if we can't do that that's to and disable it from replicating. |
|
| 40:45 | , that, that drug was that drug was, has been around |
|
| 40:48 | a long time. Uh, almost probably nearly 30 something years. |
|
| 40:54 | one of the first ones when the I DS epidemic came about, |
|
| 40:57 | and they've since had to tinker with because the earth transcript base itself evolves |
|
| 41:04 | has changed somewhat. So we had change, uh, the, the |
|
| 41:08 | of a AZT that will work best it, but it, it still |
|
| 41:12 | effective. All right. Um So are you looking at this question? |
|
| 41:19 | Any, any particular questions? Oh . All right. So this is |
|
| 41:29 | of a little bit of evolution. here. OK. So within a |
|
| 41:37 | weeks of treatment with the drug, this is just a hypothetical drug. |
|
| 41:41 | don't think it's real. Uh three . A patient's HIV population consists entirely |
|
| 41:50 | three TC resistant viruses. How can result best be explained? OK. |
|
| 42:18 | . OK. Yeah. OK. app for 10, 9. |
|
| 43:16 | So, um no, the, like I said, it's kind of |
|
| 43:26 | one on one. OK. um in this instance, uh drug |
|
| 43:33 | types or whether it's um it could the evolution of some feature of |
|
| 43:41 | an animal in a population somewhere. . Um The, the uh environmental |
|
| 43:51 | , OK. What we call selective , OK. The conditions themselves provide |
|
| 43:59 | of the incubator to allow those that have changes. OK? That's why |
|
| 44:06 | is so important in population, If you have lots of variation, |
|
| 44:11 | means everybody is slightly different, not , right? And can potentially |
|
| 44:19 | you know, when things change out , OK? If everybody were the |
|
| 44:24 | clones completely, you basically just respond sync with each other, good or |
|
| 44:30 | . OK? But because we have , right? There is a not |
|
| 44:35 | chance that there would be a subset will be better able to handle that |
|
| 44:41 | , right? And so it then . And so that's why uh variation |
|
| 44:47 | reproduction, right? So those members are better surviving, reproduce, |
|
| 44:55 | Uh better. And their numbers take eventually. OK. Um As long |
|
| 45:01 | that trait is, is, is beneficial, continues to be beneficial. |
|
| 45:08 | ? Then those members are better able survive and they will proliferate. |
|
| 45:13 | So the point is it's already right? The change is already |
|
| 45:17 | Nothing's making it, right? Uh , but it's already present in the |
|
| 45:22 | and that's why B is the right here. OK. So you got |
|
| 45:30 | drug resistant types already there, They don't know they're drug resistant yet |
|
| 45:35 | the conditions show up to favor their . OK. So um the drug |
|
| 45:43 | cause it, but rather, or the drug, the HIV didn't begin |
|
| 45:48 | making drug resistant versions. OK? , the changes are already present. |
|
| 45:53 | ? And just the, the, , the presence of the um of |
|
| 45:58 | drug is what enforced their hand, know? OK. II I have |
|
| 46:04 | variants here that can survive this. now I can grow, right? |
|
| 46:07 | other people around me can't, they have that change that I do. |
|
| 46:12 | . So, I mean, that's just, not just this example, |
|
| 46:17 | across the whole world, how evolution the same way. OK? You |
|
| 46:21 | members in the population that potentially can maybe AAA change in the environment and |
|
| 46:30 | will proliferate. OK. Um Any about that? Yeah, that's why |
|
| 46:37 | is a good thing. OK. enables better chance of surviving. |
|
| 46:44 | Um So um turning the turning the perspective now to goodness, sorry about |
|
| 46:57 | . That was horrific. OK. . Absolutely. That scared me. |
|
| 47:03 | right. OK. Um God. All right. OK. So |
|
| 47:10 | So um we were talking about how kill them and different targets we |
|
| 47:15 | but of course, we're all well of antibiotic resistance. And so the |
|
| 47:21 | mechanisms that are used to, we to kill them different targets. |
|
| 47:25 | obviously, it's changing changes in those targets that uh provide resistance. So |
|
| 47:32 | kind of a, a basic 101 how this happens. OK. So |
|
| 47:43 | this is kind of a, a bit dramatic here if you ask |
|
| 47:46 | but here comes a um antibiotic, say that pathogen is resistant and this |
|
| 47:56 | blows up, right? That's kind a dramatic. OK. Um In |
|
| 48:01 | case, um so here it goes the a particular population, right? |
|
| 48:07 | you already have in the population, yellow ones that, that have a |
|
| 48:13 | that enables them to survive a particular . So others die and they |
|
| 48:19 | they can proliferate. Um That's the of this. OK. And so |
|
| 48:28 | the thing is you have to have presence of antibiotic there to flesh these |
|
| 48:35 | out, right? So this just you kind of we talked about this |
|
| 48:40 | , the different types of mutations that in these changes. Ok. So |
|
| 48:45 | it can be producing a an enzyme might destroy the antibiotic. Um the |
|
| 48:52 | about this as well, horizontal gene , right? How we can pass |
|
| 48:55 | these traits to uh how we can on to, to other cells. |
|
| 49:00 | Not just necessarily the same species, be too closely related species, |
|
| 49:06 | Page can be a part of They can transfer these traits as well |
|
| 49:10 | uh transduction. Um And so the and so back to conjugation as |
|
| 49:18 | So back to this picture here Ah here. All right. Um |
|
| 49:34 | wanted no, go back. Here. The resistant ones are in |
|
| 49:41 | , right? So we don't even them until we apply that selective |
|
| 49:46 | right? So this kind of goes misuse of antibiotics, right? So |
|
| 49:52 | antibiotics everywhere. I mean, in food uh I guarantee you can sample |
|
| 49:59 | , the, the sewer water and gonna be full of antibiotics. |
|
| 50:03 | certainly that, you know, we antibiotics in the cattle and chicken |
|
| 50:07 | you know, uh, other animals we eat, we, as they |
|
| 50:11 | up, we give them antibiotics because you're in crowded conditions, like how |
|
| 50:15 | typically grow these factory farms, that's breeding ground for spreading disease very |
|
| 50:21 | Right. When you're so crowded So they come full of antibiotics to |
|
| 50:26 | spread of disease. Um, same the fish, fish farms. Same |
|
| 50:31 | they are. Um, they're grown lot large density. So very |
|
| 50:36 | You give fish antibiotics too for the purpose. So, uh, so |
|
| 50:40 | ingest this, you ingest antibiotics even you're not sick. Right. But |
|
| 50:44 | providing selective pressure now for types in body to become resistant. Right. |
|
| 50:51 | that's why just, you know, of antibiotics is so bad and it |
|
| 50:56 | to, um, to this problem , of resistance. Ok. |
|
| 51:02 | and I get that, you you go to, uh, one |
|
| 51:06 | these emergency room clinics, right? it's full of people and they're coughing |
|
| 51:10 | this and that, and they're sick there's like one doctor working there for |
|
| 51:14 | 100 patients. And, I you're not gonna bother to isolate the |
|
| 51:17 | of every person and, you get the right antibiotics. So, |
|
| 51:20 | do you do? You're right. , broad spectrum there go. |
|
| 51:23 | And of course, that can, can take care of your infection, |
|
| 51:27 | it can also, you know, this problem as well with other types |
|
| 51:32 | that are nearby. So it's uh mean, obviously you wanna be |
|
| 51:37 | personal well again, but it does to this kind of problem. |
|
| 51:43 | Um persist cells. So these are that um good example of this are |
|
| 51:50 | types that you um you, so take antibiotic, OK. And so |
|
| 51:55 | most antibiotics, they're most effective when target bacteria, let's say, are |
|
| 52:03 | growing, OK? They're actively growing of the target is present or is |
|
| 52:10 | at all when they're actively growing. that's when antibiotics affect, right? |
|
| 52:14 | there are cell types that in the of antibiotic when they sense it, |
|
| 52:19 | can say who slow down. I'm gonna grow. I'm just gonna sit |
|
| 52:24 | , I'm gonna wait. All And that's what a persist. That's |
|
| 52:27 | strategy of a persist cell is. just say, OK, I can |
|
| 52:31 | antibiotics here. I'm just gonna sit , hunker down and not grow at |
|
| 52:35 | . If I do that, it affect me. And that and that |
|
| 52:39 | . And so uh because you take antibiotic, it doesn't linger in your |
|
| 52:45 | , you know, forever it, goes away. And so that's the |
|
| 52:49 | when they then begin to grow. . So very uh sneaky, um |
|
| 52:55 | bugs, those are just multi resistant . So you can have types that |
|
| 52:59 | resistant to one type of antibiotic. you have types that have multiple resistances |
|
| 53:05 | of course, are even obviously Uh micro uh tuberculosis bacterium is, |
|
| 53:11 | , there's several of those that are the super mug category, res resistant |
|
| 53:14 | multiple three or four or five Um The uh we talked about that |
|
| 53:22 | it's certainly gonna spread through conjugation, , et cetera. And so here |
|
| 53:29 | different mechanisms of, let me the on this guy. Sorry, they |
|
| 53:39 | . OK. OK. Do it . All right. OK. So |
|
| 53:44 | penicillin. All right. So uh kind of penicillin there is a beta |
|
| 53:51 | enzyme that basically just blows it OK. And uh obviously penicillin has |
|
| 53:58 | effect if it's being destroyed. Um The uh uh the next one |
|
| 54:07 | , forget the order. OK. , um uh manipulating the, |
|
| 54:12 | of course, antibiotics have to get the cell. So if you can |
|
| 54:15 | of interfere with their entry into the , then that can be a |
|
| 54:20 | OK. Um So alter the, transport protein that comes in to not |
|
| 54:26 | it come in anymore. OK. Interfering with uh so you can |
|
| 54:31 | we saw this with the uh interfering a metabolite production by competing with an |
|
| 54:36 | . Well, maybe the enzyme OK. And mutation occurs, enzyme |
|
| 54:42 | , it still, it works. now it uh it doesn't, it |
|
| 54:46 | bind the antibiotics. So now it's antibiotics rendered ineffective. So changing, |
|
| 54:51 | the target molecule is a strategy. . Um You can um that's for |
|
| 54:59 | a little bit, you can uh flux pump is another common one. |
|
| 55:03 | , antibiotic that comes in, we pump it out, right? That's |
|
| 55:07 | , that's a common uh resistance mechanism to get it out, pump it |
|
| 55:11 | . Um The uh I think that's . So we summarize these oop. |
|
| 55:20 | that. Mm uh Let's go OK. Yeah. So this is |
|
| 55:26 | of a summary of all those So again, this simply destroy, |
|
| 55:32 | the antibiotic um by leaving it or have you uh change the, |
|
| 55:40 | the, the, the target itself terms of shape. So, you |
|
| 55:43 | , proteins are all about shape when bind specific shapes. And so if |
|
| 55:47 | change the shape of it, it certainly uh now not bind to the |
|
| 55:53 | . OK. Uh Pumping them E flex means to pump out, |
|
| 55:58 | ? Um The uh um blocking entry well. So alter the, |
|
| 56:05 | the, the transfer protein through which comes and now it can't, can't |
|
| 56:09 | in. OK. So uh and could be, it could be multiple |
|
| 56:13 | these. It can 11 strain can two or more of these if it's |
|
| 56:17 | of those super bugs. OK. here it shows you um you know |
|
| 56:22 | , how quickly this can happen in cases. OK. So we have |
|
| 56:27 | antibiotic therapy occurring here. So we numbers of bacteria per mill on Y |
|
| 56:34 | days here and uh we initiate antibiotic . Um And uh here is resistance |
|
| 56:45 | line this axis. So, you , they're, they're not resistant, |
|
| 56:50 | then you see the eventual beginnings of types growing, OK. And then |
|
| 56:58 | eventually they're taking it over. So this is over the course of |
|
| 57:03 | 11 days. OK. And um so it's, it's, it's |
|
| 57:08 | real uh problem uh that you'll certainly in the world of health care. |
|
| 57:16 | , um it's, you know, things to be done, obviously. |
|
| 57:23 | when you can isolate the culture, it's possible, uh it doesn't, |
|
| 57:28 | don't necessarily have to get on the , you know, that that can |
|
| 57:31 | take some time, but you can least ID it through I immunological methods |
|
| 57:36 | quickly then that can at least give a better handle on the specific antibiotics |
|
| 57:41 | use. So just throwing this broad all the time, right? Make |
|
| 57:46 | more specific or at least narrow it . So um but yeah, I |
|
| 57:52 | , it again, everything evolves and so the passengers and, and their |
|
| 57:56 | to get around um antibiotics and, your immune system. So, uh |
|
| 58:03 | see any questions on any folks, ? Questions, questions. OK. |
|
| 58:11 | uh we'll remember the exam starts tomorrow Saturday, Friday, Saturday. And |
|
| 58:23 | finish this |
|
