7 ms·

What about decreasing pulmonary vasodilation? Wouldn't pulmonary hypertension be beneficial here? Is this a role zinc might play? If there is a zinc deficiency

by podgaj 7y ago

What about decreasing pulmonary vasodilation? Wouldn't pulmonary hypertension be beneficial here? Is this a role zinc might play? If there is a zinc deficiency would this not lead to vasodialtion and the dilution of the pneumocytes? https://www.frontiersin.org/articles/10.3389/fphys.2018.00641/full https://www.frontiersin.org/articles/10.3389/fphys.2018.0064... Further evidence for abnormal iron handling was demonstrated by Decker et al. (2011) who showed that zinc protoporphyrin (Zn-pp) levels are high in patients with PAH (mainly iPAH) indicating deficient iron incorporation to form heme suggestive of iron deficiency; levels were closely related to clinical severity (Decker et al., 2011). Zinc competes with iron for binding sites, therefore when iron levels are diminished zinc replaces iron at these sites. PAH patients also had a high red cell distribution width (RDW), again corresponding to markers of clinical severity, such as higher pulmonary arterial pressures and lower 6MWT. Most recently, using proteome analysis in the plasma of patients with PAH, Rhodes et al. (2017) were able to identify a combination of nine circulating proteins associated with a high risk of mortality, two of which, plasminogen and erythropoietin, are associated with abnormal iron metabolism (Rhodes et al., 2017).

podgaj 7y ago
Why am I being down voted for a question? Sorry I am old and new to Hacker News but I have a Phd. Am I doing something wrong?
- nitrogen 7y ago
  Welcome to HN! I'm not an expert on the subject, nor am I anybody important here, but give it time. Sometimes downvotes are accidental, sometimes it takes a while for a refutation to make it clear what was wrong, sometimes you just never find out. Best to just take it in stride as something random until more information is available.
  - podgaj 7y ago
    Thanks!
    - PopeDotNinja 7y ago
      You can add a blurb about your credentials to help with down votes. For example, lead with "I have a PhD in <subject>" when your creds are applicable to the case you're trying to make. Also, votes are just fake internet points. No need to worry about them too much :)
- w3mmpp 7y ago
  You're most likely penalized for some kind of wrongthink, don't worry about it. Upvoted.
- j45 7y ago
  There is a lot more drive by downvoting than there used to be. It takes an open mind to openly entertain a viewpoint that isn’t ones own. Also takes an open mind to say just because I don’t understand/agree with something, it doesn’t mean there can’t be understanding in it.
  - podgaj 7y ago
    I would suggest that any down or up votes must be accompanied with a reason and reply then, yes? Or maybe just get rid of the voting and let the comments speak for themselves.
    - Mountain_Skies 7y ago
      Drive-by downvoting of quality or interesting comments usually are offset by upvotes in any marginally popular post. Don't worry about it. Points here mean much less than they do on sites like Stack Overflow and Reddit.
      - j45 7y ago
        Not worried at all .. OP had lamented. In terms of the type of behaviour that should be encouraged on YC.. celebrating a diversity of understanding, belief and practice should be OK in a community of individuals wanting to build things that are different. OP had reflected out loud :)
    - j45 7y ago
      That would be interesting. Maybe also limiting the number of downvotes per period.
  - malandrew 7y ago
    The drive by downvoting is out of control. I wish they changed it from a threshold of 500 to a threshold of 500 and you’re only allowed to downvote accounts that came after you until you get to like 2000 points or something like that. Basically we need a mechanism to mitigate the impact of eternal September. There are too many new people with downvote ability changing the culture here for the worse. What’s insane is the number of times I see people downvoted for simply asking for sources/citations/references/ evidence/etc.
- dodgyb 7y ago
  podgaj - have you checked out https://www.reddit.com/r/COVID19/ https://www.reddit.com/r/COVID19/? It a well moderated discussion thread focused solely on the science. You will find it a little saner there.
DoreenMichele 7y ago
On the surface, this comment appears to contradict something you said to me elsewhere. Wouldn't this process fit with what I was asking about heme involvement and some sort of disruption of the oxygen pathway? Can anyone else chime in on that idea?
- podgaj 7y ago
  I was speaking about your inquiry into the damage to the heart and I felt that oxidative stress could better explain that damage. Zinc replacing the iron in heme might help in the lungs. Both aspects would involve a zinc deficiency.
  - DoreenMichele 7y ago
    Then there's a been a miscommunication somewhere. I did my best to talk about some sort of disruption to the pathway involving oxygen uptake and utilization. I'm a layman, so I'm maybe not phrasing it the best way. But I'm getting the impression that the reason ventilators are failing so badly is because it's not treating the right problem. I have this idea that the infection is interfering with the oxygen pathway -- with how red blood cells take on and/or utilize oxygen. If that's the problem, more oxygen won't do much. If the body can't absorb it, extra supplies of oxygen just won't really take. Can anyone speak to that idea in layman's terms with regards to what is known about the pathology of this class of infection? Edit: I'm talking about a process similar to anemia or altitude sickness. I'm talking about some barrier to the body adequately using oxygen, in addition to any other challenges like fluid in the lungs blocking oxygen uptake. Info on dietary sources of zinc: https://www.healthline.com/nutrition/best-foods-high-in-zinc#section9 https://www.healthline.com/nutrition/best-foods-high-in-zinc...
    - podgaj 7y ago
      The hypoxia issue is more of a physical problem caused by inflammation. Think about trying to push a marble through plastic, that is what the vents are trying to do with the oxygen that is trying to get from the aveoli to the capillary. Vents are not a treatment, they are support. Treatment would either slow replication or lower the inflammation. But I like your thinking.
carbocation 7y ago
Why would pulmonary hypertension, which increases RV afterload and can contribute to shock, be beneficial? What evidence do you have that zinc deficiency, rather than an infection causing a global pandemic, is causing hypoxemic respiratory failure right now? To me, these seem totally irrelevant to COVID, but can you elaborate a direct connection?
- podgaj 7y ago
  I was just using the PAH as an example, but the issue in the lungs results from vasodilation (please correct me anyone if I am wrong). So vasocontriction might slow the leaking of fluid into the intercistal space. Regarding the zinc deficiency; we see a large variation in outcomes after infection. Part could be viral load, but since we know people with "comorbidities" are more vulnerable to bad outcomes this delta should be an area of interest. Some people are totally asymptomatic! The comorbidities (let's say heart disease) are caused by environmental or genetic variables. It seems zinc deficiency, to me, might be a common thread to both comorbidity and infection outcomes. Since ACE2, a zinc metalloprotein which uses zinc as a cofactor, is in the alveoli and is the receptor for the virus, it would make sense to look at this as a serious possibility. ACE2 is a "Therapeutic Target for Heart Failure" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944399/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944399/ And zinc plays a role in the lung disease as well: https://link.springer.com/article/10.1007/BF00944606 https://link.springer.com/article/10.1007/BF00944606 Interleukin-1α (IL-1α) production by alveolar macrophages in patients with acute lung diseases: the influence of zinc supplementation "These results suggest that zinc can regulate the production of IL-1α from AM in patients with pulmonary tuberculosis or bacterial pneumonia." Both anecdotally and experimentally there is evidence that zinc inhibits the replication of several virii. So zinc deficiency might make infection more likely and weaken the immune system to make outcome worse.
  - carbocation 7y ago
    It's fine to speculate, but there is no real connection between these ideas and COVID beyond pure speculation. Vasodilation is not the issue with the lungs (unless you mean V/Q mismatch for specific vascular beds, in which case this is the accepted dogma and is unrelated to pulmonary hypertension). The other hypotheses are at the level of preclinical evidence. Some (e.g., zinc deficiency being a common cause of causing heart disease) would upend all known clinical data.

by podgaj 7y ago

podgaj 7y ago

Why am I being down voted for a question? Sorry I am old and new to Hacker News but I have a Phd. Am I doing something wrong?

nitrogen 7y ago
Welcome to HN! I'm not an expert on the subject, nor am I anybody important here, but give it time. Sometimes downvotes are accidental, sometimes it takes a while for a refutation to make it clear what was wrong, sometimes you just never find out. Best to just take it in stride as something random until more information is available.
- podgaj 7y ago
  Thanks!
  - PopeDotNinja 7y ago
    You can add a blurb about your credentials to help with down votes. For example, lead with "I have a PhD in <subject>" when your creds are applicable to the case you're trying to make. Also, votes are just fake internet points. No need to worry about them too much :)
w3mmpp 7y ago
You're most likely penalized for some kind of wrongthink, don't worry about it. Upvoted.
j45 7y ago
There is a lot more drive by downvoting than there used to be. It takes an open mind to openly entertain a viewpoint that isn’t ones own. Also takes an open mind to say just because I don’t understand/agree with something, it doesn’t mean there can’t be understanding in it.
- podgaj 7y ago
  I would suggest that any down or up votes must be accompanied with a reason and reply then, yes? Or maybe just get rid of the voting and let the comments speak for themselves.
  - Mountain_Skies 7y ago
    Drive-by downvoting of quality or interesting comments usually are offset by upvotes in any marginally popular post. Don't worry about it. Points here mean much less than they do on sites like Stack Overflow and Reddit.
    - j45 7y ago
      Not worried at all .. OP had lamented. In terms of the type of behaviour that should be encouraged on YC.. celebrating a diversity of understanding, belief and practice should be OK in a community of individuals wanting to build things that are different. OP had reflected out loud :)
  - j45 7y ago
    That would be interesting. Maybe also limiting the number of downvotes per period.
- malandrew 7y ago
  The drive by downvoting is out of control. I wish they changed it from a threshold of 500 to a threshold of 500 and you’re only allowed to downvote accounts that came after you until you get to like 2000 points or something like that. Basically we need a mechanism to mitigate the impact of eternal September. There are too many new people with downvote ability changing the culture here for the worse. What’s insane is the number of times I see people downvoted for simply asking for sources/citations/references/ evidence/etc.
dodgyb 7y ago
podgaj - have you checked out https://www.reddit.com/r/COVID19/ https://www.reddit.com/r/COVID19/? It a well moderated discussion thread focused solely on the science. You will find it a little saner there.

DoreenMichele 7y ago

On the surface, this comment appears to contradict something you said to me elsewhere. Wouldn't this process fit with what I was asking about heme involvement and some sort of disruption of the oxygen pathway? Can anyone else chime in on that idea?

podgaj 7y ago
I was speaking about your inquiry into the damage to the heart and I felt that oxidative stress could better explain that damage. Zinc replacing the iron in heme might help in the lungs. Both aspects would involve a zinc deficiency.
- DoreenMichele 7y ago
  Then there's a been a miscommunication somewhere. I did my best to talk about some sort of disruption to the pathway involving oxygen uptake and utilization. I'm a layman, so I'm maybe not phrasing it the best way. But I'm getting the impression that the reason ventilators are failing so badly is because it's not treating the right problem. I have this idea that the infection is interfering with the oxygen pathway -- with how red blood cells take on and/or utilize oxygen. If that's the problem, more oxygen won't do much. If the body can't absorb it, extra supplies of oxygen just won't really take. Can anyone speak to that idea in layman's terms with regards to what is known about the pathology of this class of infection? Edit: I'm talking about a process similar to anemia or altitude sickness. I'm talking about some barrier to the body adequately using oxygen, in addition to any other challenges like fluid in the lungs blocking oxygen uptake. Info on dietary sources of zinc: https://www.healthline.com/nutrition/best-foods-high-in-zinc#section9 https://www.healthline.com/nutrition/best-foods-high-in-zinc...
  - podgaj 7y ago
    The hypoxia issue is more of a physical problem caused by inflammation. Think about trying to push a marble through plastic, that is what the vents are trying to do with the oxygen that is trying to get from the aveoli to the capillary. Vents are not a treatment, they are support. Treatment would either slow replication or lower the inflammation. But I like your thinking.

carbocation 7y ago

Why would pulmonary hypertension, which increases RV afterload and can contribute to shock, be beneficial? What evidence do you have that zinc deficiency, rather than an infection causing a global pandemic, is causing hypoxemic respiratory failure right now? To me, these seem totally irrelevant to COVID, but can you elaborate a direct connection?

podgaj 7y ago
I was just using the PAH as an example, but the issue in the lungs results from vasodilation (please correct me anyone if I am wrong). So vasocontriction might slow the leaking of fluid into the intercistal space. Regarding the zinc deficiency; we see a large variation in outcomes after infection. Part could be viral load, but since we know people with "comorbidities" are more vulnerable to bad outcomes this delta should be an area of interest. Some people are totally asymptomatic! The comorbidities (let's say heart disease) are caused by environmental or genetic variables. It seems zinc deficiency, to me, might be a common thread to both comorbidity and infection outcomes. Since ACE2, a zinc metalloprotein which uses zinc as a cofactor, is in the alveoli and is the receptor for the virus, it would make sense to look at this as a serious possibility. ACE2 is a "Therapeutic Target for Heart Failure" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944399/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944399/ And zinc plays a role in the lung disease as well: https://link.springer.com/article/10.1007/BF00944606 https://link.springer.com/article/10.1007/BF00944606 Interleukin-1α (IL-1α) production by alveolar macrophages in patients with acute lung diseases: the influence of zinc supplementation "These results suggest that zinc can regulate the production of IL-1α from AM in patients with pulmonary tuberculosis or bacterial pneumonia." Both anecdotally and experimentally there is evidence that zinc inhibits the replication of several virii. So zinc deficiency might make infection more likely and weaken the immune system to make outcome worse.
- carbocation 7y ago
  It's fine to speculate, but there is no real connection between these ideas and COVID beyond pure speculation. Vasodilation is not the issue with the lungs (unless you mean V/Q mismatch for specific vascular beds, in which case this is the accepted dogma and is unrelated to pulmonary hypertension). The other hypotheses are at the level of preclinical evidence. Some (e.g., zinc deficiency being a common cause of causing heart disease) would upend all known clinical data.