some random questions/discrepancys

[westernmed007]

Did some questions today, had a lots of questions of my own aftewards, looked up most of them, puzzled by these few: (if you answer if possibly could you state your source?)

1) Question I had today said that D-Ala D-Ala is what is inhibited by PCN, (I thought it did D-glu D-glu) FA says that this is what Vancomycin targets. Do PCN's and Vancyomycin target the exact same thing?
(couldn't find answer to that one in MBMRS or FA or wiki)


2) I know insulin is a tyrosine kinase receptor, one question I had said it did do the MAP pathway and the other one said that it didn't.....

3) Sepsis: Lipid A- IL 1, 6, TNF A (acute phase)
Superantigens (toxic shock)- stim T cell receptor (releases IL 2, INF G) and MHC on macros - (releases IL 1 and TNF A)

Does that make sense? (ps is scalded skin syndrome a superantigen?)

4) Granuloma Inguinale vs Lymphogranuloma venereum vs Chancroid- how on earth do you tell these apart clinically, the various questions I have seen seem to focus on minutiae that almost seem like buzz words
(ie LV and "inclusion bodies" even though you also have inclusions in G.Inguinale, so frustrating).

Thanks for any help you can give me, these questions have bugged me for the last 2 hours and I can't seem to get them straight, any help would be appreciated.

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[westernmed007]

Anyone? or is this going down in flames like my alkylation vs intercalation question (which I still don't know)....

 

[virilep]

Did some questions today, had a lots of questions of my own aftewards, looked up most of them, puzzled by these few: (if you answer if possibly could you state your source?)

1) Question I had today said that D-Ala D-Ala is what is inhibited by PCN, (I thought it did D-glu D-glu) FA says that this is what Vancomycin targets. Do PCN's and Vancyomycin target the exact same thing?
(couldn't find answer to that one in MBMRS or FA or wiki)

I can do 1.
Vancomycin targets transglyosylation and PCN is a Beta Lactam that targets transpeptidation. (in the steps to build a cell wall).

They both target D-Ala D-Ala but they target different steps of those substrates.

 

[___Doctor786___]

Did some questions today, had a lots of questions of my own aftewards, looked up most of them, puzzled by these few: (if you answer if possibly could you state your source?)

1) Question I had today said that D-Ala D-Ala is what is inhibited by PCN, (I thought it did D-glu D-glu) FA says that this is what Vancomycin targets. Do PCN's and Vancyomycin target the exact same thing?
(couldn't find answer to that one in MBMRS or FA or wiki)


2) I know insulin is a tyrosine kinase receptor, one question I had said it did do the MAP pathway and the other one said that it didn't.....

3) Sepsis: Lipid A- IL 1, 6, TNF A (acute phase)
Superantigens (toxic shock)- stim T cell receptor (releases IL 2, INF G) and MHC on macros - (releases IL 1 and TNF A)

Does that make sense? (ps is scalded skin syndrome a superantigen?)

4) Granuloma Inguinale vs Lymphogranuloma venereum vs Chancroid- how on earth do you tell these apart clinically, the various questions I have seen seem to focus on minutiae that almost seem like buzz words
(ie LV and "inclusion bodies" even though you also have inclusions in G.Inguinale, so frustrating).

Thanks for any help you can give me, these questions have bugged me for the last 2 hours and I can't seem to get them straight, any help would be appreciated.

I will take a shot at it, but I'm a first year, so take my answers with a grain of salt. The way I understand it, Penicillins inhibit transpeptidase reactions in the peptidoglycan wall. Bacterias have several modes of resistances and one of the modes of resistance to the penicillins is Beta-lectamases (which cleave the weakest bond of beta-lactames). Remember that Penicillins do not work on Methicillin resistant SA (MRSA), so Vancomycin is used instead, which works by inhibiting the transglycosylation reactions (D-ala D-ala sequences), and the bacterias are developing resistance to it by changing the sequence to D-ala D-lactate.

Scalded skin sydrome is caused by exfolatins of the staphylococcus aureus, and I'm not 100% sure, but I don't think it's a superantigen. The superantigen is the toxic shock syndrome toxin-1, also produced by SA, which causes Toxic Shock Syndrome.

Hope it helps!

 

[Blesbok]

Did some questions today, had a lots of questions of my own aftewards, looked up most of them, puzzled by these few: (if you answer if possibly could you state your source?)

1) Question I had today said that D-Ala D-Ala is what is inhibited by PCN, (I thought it did D-glu D-glu) FA says that this is what Vancomycin targets. Do PCN's and Vancyomycin target the exact same thing?
(couldn't find answer to that one in MBMRS or FA or wiki)
Vancomycin targets d-ala-d-ala, but it is not an analog. It is resisted by changing from d-ala-d-ala to d-ala-d-glu. Penicillin is actually an analog of d-ala-d-ala that inhibits it by competitive antagonism of cell wall formation.


2) I know insulin is a tyrosine kinase receptor, one question I had said it did do the MAP pathway and the other one said that it didn't.....
I always had trouble with this exact problem and I think it activates protein kinase B through means other than the MAPK pathway, but don't quote me on it as I have yet to find a good definitive source.

3) Sepsis: Lipid A- IL 1, 6, TNF A (acute phase)
Superantigens (toxic shock)- stim T cell receptor (releases IL 2, INF G) and MHC on macros - (releases IL 1 and TNF A)

Does that make sense? (ps is scalded skin syndrome a superantigen?)
Sounds about right.

4) Granuloma Inguinale vs Lymphogranuloma venereum vs Chancroid- how on earth do you tell these apart clinically, the various questions I have seen seem to focus on minutiae that almost seem like buzz words
(ie LV and "inclusion bodies" even though you also have inclusions in G.Inguinale, so frustrating).
I doubt you will see any of these on boards (maybe lymphogranuloma or chancroid, but I doubt it). Know that granuloma inguinale and lymphogranuloma are painless (at least initially) and that inguinale forms nodules more than ulcers. Also, chancroid is painful. Finally, know what causes each one.

Thanks for any help you can give me, these questions have bugged me for the last 2 hours and I can't seem to get them straight, any help would be appreciated.

.

 

[medstu2006]

Vancomycin targets d-ala-d-ala, but it is not an analog. It is resisted by changing from d-ala-d-ala to d-ala-d-glu.

Just a quick correction. Vancomycin resistance is caused by the change of D-ala-D-ala to D-ala-D-lac not D-ala-D-glu.

 

[Monica Lewinsky]

Insulin works through a MAP Kinase pathway and a PI3K pathway.

 

[indo]

Penicillin and all the beta lactams are D-ala-D-ala analogs. This means that they act on the PBPs by looking like the cell wall.

Vancomycin actually binds to the D-ala-D-ala so the PBPs can get in there and cross link.

 

[Fuzuli]

1) Question I had today said that D-Ala D-Ala is what is inhibited by PCN, (I thought it did D-glu D-glu) FA says that this is what Vancomycin targets. Do PCN's and Vancyomycin target the exact same thing?
(couldn't find answer to that one in MBMRS or FA or wiki)

Beta-lactam antibiotics, structural analogs of the natural D-Ala-D-Ala substrate, covalently bind to the active site of PBPs. This inhibits the transpeptidation reaction; halting peptidoglycan synthesis and the cell dies. The exact mechanism of cell death is not completely understood, but autolysins and disruption of cell wall morphogenesis are involved. Penicillins and cephalosporins kill bacterial cells only when they are actively growing and synthesizing cell wall.

Vancomycin inhibits cell wall synthesis by binding firmly to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide. This inhibits the transglycosylase, preventing further elongation of peptidoglycan and cross-linking. The peptidoglycan is thus weakened, and the cell becomes susceptible to lysis. The cell membrane is also damaged, which contributes to the antibacterial effect.

("Beta-Lactam & Other Cell Wall and Membrane Active Antibiotics", Basic and Clinical Pharmacology, 10th Edition, 2006)

So basically:

• Penicillins: Bind to PBPs; inhibit transpeptidase which cross-links linear peptidoglycan chains that form bacterial cell wall; activate autolytic enzymes and causes lysis of the bacterial cell
• Vancomycin: Binds to D-Ala-D-Ala terminal of the peptidoglycan side chain; inhibits transglycosylation which prevents elongation of the peptidoglycan chain and interferes with cross-linking

2) I know insulin is a tyrosine kinase receptor, one question I had said it did do the MAP pathway and the other one said that it didn't.....

Insulin binding to its receptor stimulates intrinsic tyrosine kinase activity, leading to receptor autophosphorylation and the recruitment of intracellular signaling molecules, such as insulin receptor substrates (IRS). IRS and other adaptor proteins initiate a complex cascade of phosphorylation and dephosphorylation reactions, resulting in the widespread metabolic and mitogenic effects of insulin. As an example, activation of the phosphatidylinositol-3'-kinase (PI-3-kinase) pathway stimulates translocation of glucose transporters (e.g., GLUT4) to the cell surface, an event that is crucial for glucose uptake by skeletal muscle and fat. Activation of other insulin receptor signaling pathways induces glycogen synthesis, protein synthesis, lipogenesis, and regulation of various genes in insulin-responsive cells.

("Diabetes Mellitus", Harrison's Principles of Internal Medicine, 17th Edition, 2008)

Role of insulin in glycogen metabolism:

("Insulin", The Medical Biochemistry Page, http://themedicalbiochemistrypage.org/insulin.html, Accessed on May 1st, 2008)

So basically, it depends on which action of insulin you're referring to. In glycogen metabolism, MAPK pathway is used; whereas in protein synthesis (e.g. GLUT-4), insulin induces PI3K/PIP3/PDK pathway, which eventually effects mTOR.

3) Sepsis: Lipid A- IL 1, 6, TNF A (acute phase)
Superantigens (toxic shock)- stim T cell receptor (releases IL 2, INF G) and MHC on macros - (releases IL 1 and TNF A)

Does that make sense? (ps is scalded skin syndrome a superantigen?)

Toxic shock syndrome results from the ability of enterotoxins and toxic shock syndrome toxin 1 (TSST-1) to function as T cell mitogens. In the normal process of antigen presentation, the antigen is first processed within the cell, and peptides are then presented in the major histocompatibility complex (MHC) class II groove, initiating a measured T cell response. In contrast, enterotoxins bind directly to the invariant region of MHC—outside the MHC class II groove. The enterotoxins can then bind T cell receptors via the vB chain, resulting in a dramatic overexpansion of T cell clones (up to 20% of the total T cell population).

The consequence of this T cell expansion is a "cytokine storm", with the release of inflammatory mediators that include interferon (IFN)-Y , IL-1, IL-6, TNF-a, and TNF-b. The resulting multisystem disease produces a constellation of findings that mimic those in endotoxin shock; however, the pathogenic mechanisms differ. It has been hypothesized that a contributing factor to TSS is the release of endotoxin from the gastrointestinal tract, which may synergistically enhance the toxin's effects.

The exfoliative toxins are responsible for staphylococcal scalded-skin syndrome. The toxins that produce disease in humans are of two serotypes: ETA and ETB. These toxins disrupt the desmosomes that link adjoining cells. Although the mechanism of this disruption remains uncertain, studies suggest that the toxins possess serine protease activity, which—through undefined mechanisms—triggers exfoliation. The result is a split in the epidermis at the granular level, and this event is responsible for the superficial desquamation of the skin that typifies this illness.

("Staphylococcal Infections", Harrison's Principles of Internal Medicine, 17th Edition, 2008)

• Your list is basically true, but MHC-II is not necessarily unique to macrophages; it can found on all antigen presenting cells.
• Scalded skin syndrome is caused by exfoliative exotoxins which do not have superantigenic properties.
• An example for superantigens is TSST-1, which acts as described above.

4) Granuloma Inguinale vs Lymphogranuloma venereum vs Chancroid- how on earth do you tell these apart clinically, the various questions I have seen seem to focus on minutiae that almost seem like buzz words
(ie LV and "inclusion bodies" even though you also have inclusions in G.Inguinale, so frustrating).

Although most genital ulcerations cannot be diagnosed confidently on clinical grounds alone, clinical findings plus epidemiologic considerations usually guide initial management, pending results of further tests. Clinicians should order a rapid serologic test for syphilis in all cases of genital ulcer and a dark-field or direct immunofluorescence test (or PCR test, where available) for T. pallidum in all lesions except those highly characteristic of infection with HSV (i.e., those with herpetic vesicles). All patients presenting with genital ulceration should be counseled and tested for HIV infection.



("Sexually Transmitted Infections: Overview and Clinical Approach", Harrison's Principles of Internal Medicine, 17th Edition, 2008)

I hope these explanations have answered your questions.

 

[SOUNDMAN]

Well i had a LGV question on the USMLE, on Tuesday. Had all the things, draining lymphnodes, etc. Gave you the stain and just asked you what bug it was...easy, peasy. So you want to know how the diseases present and what bug can cause them, and the treatment for those bugs.