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Sterling
Re: Viral Facts


Here is a large list of medications in trial, their target and where they are as far as study phase: Lots of Drugs


Half the the drugs on that list are anti-inflammation. Are they serious about knocking out the covid-19 virus or are they more concerned with the cytokine storm? Are there even any studies that show the anti-virals would work in vitro?

The most promising chloroquine/hydroxychloroquine stories combine it with something else and not working alone. If a study on it isn't combining it with azithromycin or zinc I don't see why any of those stories could be seen as conclusively refuted.

Have any of you heard any updates on the possible relationship of sartans and the mortality rate? Would a medicine like Micardis worsen one's chances?

Apr 4, 2020 7:29:32 AM       
Edit 3 times, last edit by Sterling at Apr 4, 2020 7:41:38 AM
Jrinne
Re: Viral Facts

Sterling,

I agree with you. The NIH needs to do some studies the drug companies will not.

With regard to azithromycin, how do you know that it is not it’s anti-inflammatory properties that are the real benefit to the combination-if the combination is in fact beneficial?

One winter I had a cough that would not go away. The ENT in the doctor’s lounge at the time and I diagnosed mycoplasma pneumonia: “walking pneumonia” being the lay term. A Z-Pak is the treatment for this.

It really, really worked well but after the second or third Z-Pak I made an appointment.

Turns out I had asthma. Azithromycin has a well documented anti-inflammatory effect the doctor I made the appointment with said, and a literature review confirmed.

All this to say that the NIH should study this as you correctly point out I think.

Also, that this could be the second time I am about to jump to a conclusion on azithromycin.

Best,

Jim

From time to time you will encounter Luddites, who are beyond redemption.
--de Prado, Marcos López on the topic of machine learning for financial applications

Apr 4, 2020 8:01:07 AM       
Edit 8 times, last edit by Jrinne at Apr 4, 2020 8:22:33 AM
Miro
Re: Viral Facts

A corollary to the definition of insanity: doing less than someone else and expecting their same results.

On the bright side, we should see the curves flatten soon in Italy, Spain and France.





Apr 4, 2020 2:43:13 PM       
Jrinne
Re: Viral Facts

Good source: COVID-19 Drug Therapy

From it, more complete and accurate information about azithromycin’s possible mechanism of action:

"Mechanism of Action: Macrolides may have immunomodulatory properties in pulmonary
inflammatory disorders. They may downregulate inflammatory responses and reduce the excessive cytokine production associated with respiratory viral infections; however, their direct effects on viral clearance are uncertain. Immunomodulatory mechanisms may include reducing chemotaxis of neutrophils (PMNs) to the lungs by inhibiting cytokines (i.e., IL-8), inhibition of mucus hypersecretion, decreased production of reactive oxygen species, accelerating neutrophil apoptosis, and blocking the activation of nuclear transcription factors.(34) (35) (36) (37)"


From time to time you will encounter Luddites, who are beyond redemption.
--de Prado, Marcos López on the topic of machine learning for financial applications

Apr 4, 2020 5:09:25 PM       
Edit 2 times, last edit by Jrinne at Apr 4, 2020 5:16:03 PM
Jrinne
Re: Viral Facts

A small controlled study of Lopinavir/Ritonavir vs chloroquine (CQ) from China: Treating COVID-19 with Chloroquine

You will not be able to miss "uncorrected manuscript."

As a separate point, I think Lopinavir/Ritonavir has already failed a clinical trial by a drug company.

I would be surprised if most institutions (in and out of the US) are not now using Remdesivir as part of an off-label protocol for severely affected hospital patients similar to the use of Lopinavir/Ritonavir at the time of the above study.

I can confirm this from Wikipedia: "…remdesivir was now available for "compassionate use" by patients that had tested positive for COVID-19; FDA Commissioner Stephen Hahn confirmed the statement at the same press conference.[28] That decision allowed physicians of COVID-19 patients to request permission to use the unapproved drug in the context of remdesivir's investigational new drug (IND) status, outside of participation in a formal clinical trial.[citation needed]"

From time to time you will encounter Luddites, who are beyond redemption.
--de Prado, Marcos López on the topic of machine learning for financial applications

Apr 5, 2020 7:17:41 AM       
Edit 6 times, last edit by Jrinne at Apr 5, 2020 7:35:08 AM
Chipper6
Re: Viral Facts

Why are hypertension and heart disease such risk factors?

Attachment CV.png (54169 bytes) (Download count: 76)


Apr 6, 2020 9:19:21 AM       
wwasilev
Re: Viral Facts

Why are hypertension and heart disease such risk factors?


I don't think there's a definitive answer yet. Here's a March 18, 2020 JAMA Q&A with Dr. Fauci. He talks about hypertension and COVID-19 starting at timestamp 10:20. I found it alarming.

https://edhub.ama-assn.org/jn-learning/video-player/18324866

Walter

Apr 6, 2020 9:36:24 AM       
Jrinne
Re: Viral Facts

Chaim,

There was an article in Lancet (widely respected journal) that asked the same question. I do not think the article had a lot of data to support this possibility but….

The ACE2 receptor probably plays a role in much of this, I think, as the article suggests. Article link: HERE

This group of people are on often ACE inhibitors. ACE stands for angiotensin-converting enzyme.

This medicine treats hypertension and any diabetic with hypertension should be using an ACE inhibitor as treatment for hypertension because the medications prevent many of the complications of diabetes including diabetic retinopathy (eye problems) and kidney problem.

From the Lancet article: "Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2) bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels."

Also of note, whatever you think of the anecdotal or early reports (from small studies) of hydroxychloriquine, the most plausible mechanism for any possible effect is that it reduces the expression of the ACE2 receptor.

Of possible personal use: many recommend Tylenol now and not ibuprofen if you have a fever as iboprofen increases the expression of the ACE2 receptor.

And honestly, I would switch medications if I were on an ACE inhibitor until they found a vaccine (e.g, calcium channel blocker). Or as the authors of the Lancet article say: "...we did not find any evidence to suggest that antihypertensive calcium channel blockers increased ACE2 expression or activity, therefore these could be a suitable alternative treatment in these patients."

CDC general information links:

Information for Clinicians on Therapeutic Options for COVID-19 Patients

CLINICAL TRIALS

Best,

Jim

From time to time you will encounter Luddites, who are beyond redemption.
--de Prado, Marcos López on the topic of machine learning for financial applications

Apr 6, 2020 9:36:31 AM       
Edit 18 times, last edit by Jrinne at Apr 6, 2020 10:54:15 AM
Chipper6
Re: Viral Facts

Also of note, whatever you think of the anecdotal or early reports (from small studies) of hydroxychloriquine, the most plausible mechanism for any possible effect is that it reduces the expression of the ACE2 receptor.
Thanks Doctor.

What do you think of the following theories?
1. Hydroxychloroquine is an ionophore, which allows zinc to enter cells more easily. (Zinc has been shown to inhibit coronavirus RNA polymerase activity in vitro.
2. Hydroxychloroquine might also affect the pH inside the cell, which might also inhibit the replication of the enzyme.

Apr 6, 2020 11:26:47 AM       
Jrinne
Re: Viral Facts

Also of note, whatever you think of the anecdotal or early reports (from small studies) of hydroxychloriquine, the most plausible mechanism for any possible effect is that it reduces the expression of the ACE2 receptor.
Thanks Doctor.

What do you think of the following theories?
1. Hydroxychloroquine is an ionophore, which allows zinc to enter cells more easily. (Zinc has been shown to inhibit coronavirus RNA polymerase activity in vitro.
2. Hydroxychloroquine might also affect the pH inside the cell, which might also inhibit the replication of the enzyme.

Chaim,

I do not have an opinion on these possible mechanisms.

Best,

Jim

From time to time you will encounter Luddites, who are beyond redemption.
--de Prado, Marcos López on the topic of machine learning for financial applications

Apr 6, 2020 12:08:08 PM       
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