Metformin with MK-677

[Stewie]

Really. Because where are those studies plastered all over the web lol.



Post valid concerns/studies that get met by pitry dish studies and over half the studies ignored with a You're wrong attitude with it. Well don't see anything proving my post are wrong.



Great follow up post. No value at all of course.



Wonder how much time both of you spend trying to refute people who post data that goes agasint your own agenda. Hey but look at this pitry dish study. And ignore 90 percent of the rest of your post and say you're wrong pal.

You do realize you posted a in-vitro murine model citation by Yaomin Chen et al. Proc Natl Acad Sci U S A. 2009."Metformin Facilitates Amyloid-β Generation by β- and γ-Secretases via Autophagy Activation."



Yet



From the full literature you cited:

Cell culture and drug treatment The human neuroblastoma cell lines SH-SY5Y andSY5Y

C99wereculturedaspreviouslydescribed [19].CellswerewashedtwiceinwarmDMEMbefore treatment with each drug at the indicated concentrations/for the indicated periods; only metformin was dissolved in DMEM supplemented with 10% fetal bovine serum (HyClone), 100 U/ml penicillin, and 100g/ml streptomycin. Doses and durations were: 2, 5, or 10mM metformin (Sigma-Aldrich, St. Louis, MO, USA) for 12 or 24h; 20M Compound C (6-[4-(2-Piperidin-1-ylethoxy)phenyl]-3-pyridin4-ylpyrazolo[1,5-a]pyrimidine) (Sigma-Aldrich, St. Louis, MO,USA)for1h(pre)treatment; 5mM3MA (3-methyladenine) (Sigma-Aldrich, St. Louis, MO, USA)for1h(pre)treatment. For cell starvation, cells were washed twice in warm DMEM and then incubated for 0.5, 1, 2, 4, or 6h.

MATERIALS AND METHODS Mice Transgenic mice (Tg6799) that overexpress both human APP 695 with the Swedish (K670N, M671L),Florida(I716V),andLondon(V717I)mutations; and mutated human (M146L and L286V), were generated. Heterozygous Tg6799 mice were intercrossed with B6/SJL mice (Taconic Farms Inc., NY, USA) to generate the desired genotypes. Mice were genotyped by PCR analysis of tail DNA; only females were used in the experiments. Age-matched female negative mice from similar crosses were used as wild-type controls. Animal care and procedures were performed in accordance with the Laboratory Animal Care Guidelines approved by Seoul National University. Drug injection/sample collection Metformin (final dose 200mg/kg)

I'll fill you in on couple of things here, Taeian.

First and foremost, in-vitro rarely if ever mimics in-vivo. in-vivo studies are useful for understanding static conditions, not so much for cellular movement(s) that occurs in breathing organisms. Yes, the citation you posted.

Secondly, we do not share the same hematological or immunological parameters as murine models. Yes, the citation you posted

Next, take a peek at the dosage(s) used 200mg/kg to induce cytotoxicity in these mice. The HED (human equivalent dose) to extrapolate murine->human the allometric scaling of 200mg/kg to that of a 90.718kg (200lb) individual, the dosage would be roughly 110,542.072mg of metformin. I'd say this would probably lead to a wee-bit more than amyloid generation.


For your pleasure and future use.
HED allometric scaling calculator:

Allometric Scaling Calculator

If you're up for learning more, don't hesitate to ask.

 

[Stewie]

You do realize you posted a in-vitro murine model citation by Yaomin Chen et al. Proc Natl Acad Sci U S A. 2009."Metformin Facilitates Amyloid-β Generation by β- and γ-Secretases via Autophagy Activation."



Yet



From the full literature you cited:







I'll fill you in on couple of things here, Taeian.

First and foremost, in-vitro rarely if ever mimics in-vivo. in-vitro literature studies are useful for understanding static conditions, not so much for cellular movement(s) that occurs in breathing organisms. Yes, the citation you posted.

Secondly, we do not share the same hematological or immunological parameters as murine models. Yes, the citation you posted

Next, take a peek at the dosage(s) used 200mg/kg to induce cytotoxicity in these mice. The HED (human equivalent dose) to extrapolate murine->human the allometric scaling of 200mg/kg to that of a 90.718kg (200lb) individual, the dosage would be roughly 110,542.072mg of metformin. I'd say this would probably lead to a wee-bit more than amyloid generation.


For your pleasure and future use.
HED allometric scaling calculator:

Allometric Scaling Calculator

If you're up for learning more, don't hesitate to ask.

Edit, typo

 

[Taeian clark]

Which study are you referring with 200mg kg dose above. Are you using hed or the mouse dose

 

[Stewie]

Are you serious??!!

I quoted the citation (abstract) you posted, I accessed the full literature.

Reread what I posted.

 

[Taeian clark]

Are you serious??!!

I quoted the citation (abstract) you posted, I accessed the full literature.

Reread what I posted.

The quotes/expanded post are not expanding on my phone.

Why are you using the mouse dose 200mg kg for hed when their respiration rate is x5? Higher then humans. The dose would be more near 4000mg not this random 100k value.

I know the difference of vitro vivo etc. Do you? Because when it fits your bias you seem to love to use vitro and correlation studies as fact all the time. Don't act like you don't give a thought of merit to certain studies on what may. Specially when you love correlation data so much which is one of weakest weights of evidence.

Plus you still ignored the rest of the studies.

 

[Stewie]

Here.

 

[Taeian clark]

Here.

No.... if mouse dose is 4mg humsn dose is 1mg. Respiration is x5 higher in mice. Your doing it wrong dont need a calc to tell you that.

 

[Stewie]

I've wasted more time with you than you're worth.

If you took the time to open that allometric scaling calculator you'd see the metabolic(s) parameters are configured in the exponents.

Geezus I feel like I'm dealing with a real argumentative dumbass.

 

[Taeian clark]

I've wasted more time with you than you're worth.

Lmao I called you out on most simplest knowledge on pharmacology and now you've wasted time cant reply anymore? Sorry but people who walk into first day any type of research field knows these values.. you really thought the mouse to human dose was 100k... you couldn't even use the calc properly let alone needed a calc...

A simple practice guide for dose conversion between animals and human

Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments. Interspecies allometric scaling for dose conversion from animal to human studies is one of ...

www.ncbi.nlm.nih.gov

 

[Stewie]

Are you truly that ignorant? The link you posted is based on the calculator I used, you, my friend are a narcissistic dumbass!

 

[Taeian clark]

Don't worry I did the math for you. The human dose for 60kg male is almost 1000mg. What planet are you on you couldn't even figure out these values its a simple divide or multiplication... yet come up with 100000. Your so far out of your field here pal.

 

[Taeian clark]

Are you truly that ignorant? The link you posted is based on the calculator I used, you, my friend are a narcissistic dumbass!

Ya and you used it wrong . How the hell do you even for a second think human dose is 100k lmao. Human dose is always lower. By about 12 times lower. Yet you got 100k and believed it lmao.. do you have any understanding of pharmacology...

 

[Stewie]

Quit while you're behind ya non-comprehensive imbecile.

 

[Taeian clark]

Quit while you're behind ya non-comprehensive imbecile.

Lmao really.. call you out once again on your sevre lack of understanding in very basic science/pharmacology and you won't even reply to it but just state im wrong.

You legit over stated the number by x100 dude... mouse numbers are always higher then human doses ratio wise due to respiration rate. And you somehow for even not just a second but this whole time thought the human dose woiud equal 100000.....
And now you won't reply but a smart remark...

 

[Stewie]

The mouse dose was 200mg/kg. Extrapolate that to a 90.718kg individual. The scaling weight for a mouse is 0.02.

Do the math.

 

[Stewie]

Do the math.

 

[Taeian clark]

The mouse dose was 200mg/kg. Extrapolate that to a 90.718kg individual. The scaling weight for a mouse is 0.02.

Do the math.

I just did and showed you... clearly you have zero understanding here of everything put into the calculations. Aka your still not understanding or mentioning one of biggest factors of respiration rate. Read the damn article lol. It gives you plenty of examples and pharmacology for dummies basically 101.. if a mouse dose is 0.4 then human dose is 0.1 mg. You seriously need to read the paper. You actually believe the dose is 100000...

This is such basic shit man..

 

[Stewie]

You are just arguing for the sake of arguing.

 

[Taeian clark]

@Swifto please explain to your buddy how horrible wrong he is. Please. Too in denial to accept hes wrong specially from someone who is so inferior like me. But cant understand this insanely basic common knowledge.

 

[Taeian clark]

You are just arguing for the sake of arguing.

Lmfao are you this delusional. Argueing for sake of argueing dude your flat out wrong and giving people 100 percent false info.

Argueing no I'm correcting you from giving 100x wrong figures. Not x2 off. But x100