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Politics : The Trump Presidency -- Ignore unavailable to you. Want to Upgrade?

To: J_F_Shepard who wrote (225105)	2/5/2022 11:12:23 PM
From: i-node	Read Replies (1) \| Respond to of 361416

>> Even the levels of ivermectin for approved human uses can interact with other medications, like blood-thinners. You can also overdose on ivermectin, which can cause nausea, vomiting, diarrhea, hypotension (low blood pressure), allergic reactions (itching and hives), dizziness, ataxia (problems with balance), seizures, coma and even death. Yes, and so half the Rx drugs known to man. WTF. This drug is one of the safest known to man, and in most countries is available without a prescription. >> Ivermectin Products for Animals Are Different from Ivermectin Products for PeopleFor one thing, animal drugs are often highly concentrated because they are used for large animals like horses and cows, which weigh a lot more than we do— up to a ton or more. Such high doses can be highly toxic in humans. Moreover, the FDA reviews drugs not just for safety and effectiveness of the active ingredients, but also for the inactive ingredients. Many inactive ingredients found in products for animals aren’t evaluated for use in people. Or they are included in much greater quantity than those used in people. In some cases, we don’t know how those inactive ingredients will affect how ivermectin is absorbed in the human body. The above paragraph reads like a label found on any drug for both human and animal consumption. The point is that FDA has withheld EUA for these two medications for one reason only: They're cheap, more effective alternatives to the expensive drugs in development (which have mostly failed) but held promise for Big Pharma. Do you not even question this? Fauci has a long history of lying about this stuff. It is bizarre. The best physicians in this country who are experts on these subjects support the use of these drugs and they have seen thousands of lives saved. And unfortunately, 100,000s of lives lost. Ivermectin is in use in 30-40% of countries, including the US. There are no reports of ivermectin causing any serious problem. Countries widely using the drug include the US, Mexico, almost all of South America, numerous reasons in Africa and MIddle East, India, Bangladesh and others, and it is believed in China. I don't know where you're getting this bullshit but I understand it. If you read the leftists in the media, you are going to take your view. It is really ridiculous that it is hard to get people to say the truth and science has been entirely lost in the process. but if you look hard you find plenty of science that shoots down your claim. Still, the dead giveaway is the very stuff you cited which is effectively FDA boilerplate.

To: J_F_Shepard who wrote (225105)	2/7/2022 10:19:09 AM
From: Thomas M.	1 Recommendation Recommended By i-node Read Replies (2) \| Respond to of 361416

Ivermectin Mechanism #1 Ivermectin blocks the virus from entering cells. ivermectin docked in the region of leucine 91 of the SARS-CoV-2 spike protein and histidine 378 of the host cell ACE-2 receptor blocking its entry into the host cell pubmed.ncbi.nlm.nih.gov Ivermectin showed 5 important docking properties: Highest binding affinity to the predicted active site of the S glycoprotein (Moldock score -140.584) and protein–ligand interactions (Moldock score -139.371). Considerable binding affinity to the predicted active site of the SARS-CoV-2 RdRp protein (Moldock score -149.9900) and protein–ligand interactions (Moldock score -147.608), it formed H-bonds with only two amino acids: Cys622 and Asp760. Highest binding affinity (Moldock score -212.265) to the predicted active site of nsp14. The highest binding affinity to the active site of the TMPRSS2 protein (Moldock score -174.971) and protein–ligand interactions (Moldock score -180.548). Moreover, it formed five H-bonds with Cys297, Glu299, Gln438, Gly462, and Gly464 amino acid residues present at the predicted active site of the TMPRSS protein. The free binding energy of the spike protein (open) was higher in ivermectin (-398.536?kJ/mol) than remdesivir (-232.973?kJ/mol). frontiersin.org Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 11:35:06 AM
From: Thomas M.	1 Recommendation Recommended By i-node Respond to of 361416

Ivermectin Mechanism #2 When cells are infected with a virus, they produce interferon to warn other nearby cells to mount their viral defenses. Covid goes into the cell nucleus and blocks production of interferon. Ivermectin blocks Covid from going into the cell nucleus. the IMPa is prevented from playing its normal role in mediating nuclear import of the STAT (signal transducer and activator of transcription) proteins in response to interferon (IFN), as part of the innate immune response (see [59]). Thus, it seems that various cytoplasmically replicating RNA viruses disrupt the cellular nuclear transport machinery in order to subvert the host cell transport processes necessary for the anti-viral response. sciencedirect.com Ivermectin's broad spectrum antiviral activity relates to its ability to target the host importin (IMP) a/ß1 nuclear transport proteins responsible for nuclear entry of cargoes such as integrase and NS5. We establish for the first time that ivermectin can dissociate the preformed IMPa/ß1 heterodimer, as well as prevent its formation, through binding to the IMPa armadillo (ARM) repeat domain to impact IMPa thermal stability and a-helicity. We show that ivermectin inhibits NS5-IMPa interaction in a cell context using quantitative bimolecular fluorescence complementation. sciencedirect.com Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 12:54:14 PM
From: Thomas M.	Read Replies (1) \| Respond to of 361416

Ivermectin Mechanism #3 Ivermectin acts as an ionophore (by chloride channel upregulation to generate apoptosis and osmotic cell death). Ionophores neutralize a virus at an early stage of the infection before it can enter the host cells. ivermectin could prove to be a powerful antiviral, therefore also useful for a possible treatment of the new coronavirus associated syndrome, even from a new perspective. This could happen assuming its role as an ionophore agent, only hinted in the recent past but never fully described (Juarez et al. 2018). Ionophores are molecules that typically have a hydrophilic pocket which constitutes a specific binding site for one or more ions (usually cations), while its external surface is hydrophobic, allowing the complex thus formed to cross the cell membranes, affecting the hydro-electrolyte balance (Freedman 2012). These chemical species have historically been used to study the mitochondrial respiratory chain and ATP synthesis in eukaryotes (in this case also known as decoupling agents, such as 2, 4-dinitrophenol), and their antibiotic activity has long been appreciated (Bakker 1979). It is also hypothesized their role as antiviral drugs (Krenn et al. 2009; Sandler et al. 2020) and anticancer chemotherapeutic agents (Kaushik et al. 2018). link.springer.com Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 1:48:55 PM
From: Thomas M.	Read Replies (2) \| Respond to of 361416

Ivermectin Mechanism #4 Nuclear transport inhibitor: Ivermectin has shown antiviral effects on RNA viruses such as Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. nature.com The integrase (IN) molecule of human immunodeficiency virus (HIV)–1 is of particular interest in this context due to its integral role in integrating the HIV genome into that of the infected host cell. Most IN-based antiviral compounds target the IN/DNA interaction, but since IN must first enter the nucleus before it can perform these critical functions, nuclear transport of IN is also an attractive target for therapeutic intervention. This study has identified ivermectin as a potential general IMP a/ß-mediated nuclear import inhibitor, which does not appear to affect nuclear import mediated by IMP ß1 alone. Although ivermectin is a broad-spectrum antiparasitic agent, which functions by modulating a7 sodium channels, the results here suggest it may also prove useful in future studies examining IMP a/ß–mediated nuclear import. journals.sagepub.com Treatment of cells with Ivermectin, an anti-parasitic drug which has been recently identified as an inhibitor of importin a/ß-dependent nuclear transport, reduced UL42 nuclear import and specifically reduced BoHV-1 replication mdpi.com Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 2:49:25 PM
From: Thomas M.	1 Recommendation Recommended By i-node Read Replies (1) \| Respond to of 361416

Ivermectin Mechanism #5 Viral RNA-dependent RNA polymerases (RdRPs) play a central role in viral replication and transcription. Ivermectin binds to RdRP and disrupts the process. Docking study showed that ivermectin is the best binding drug compared to lopinavir and simeprevir. The best binding interaction was found to be -9.7kcal/mol with RdRp suggesting potential inhibitor of the protein. researchsquare.com Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 3:08:17 PM
From: Thomas M.	Read Replies (1) \| Respond to of 361416

Ivermectin Mechanism #6 Ivermectin inhibits an enzyme which is important for viral replication: 3-chymotrypsin like protease (3CLpro) is the main protease that is pivotal for the replication of SARS-CoV-2. Our results indicate that ivermectin exhibited inhibitory effect towards 3CLpro enzymatic activity. nature.com Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 4:12:31 PM
From: Thomas M.	Read Replies (1) \| Respond to of 361416

Ivermectin Mechanism #7 Virus-infected cells release interferons to neighboring cells alerting them of a viral attack. Ivermectin promotes the expression of several interferon-related genes: the upregulation of a number of interferon responsive genes by ivermectin (ISG20, IFIT1, OASL, IRF9, IFI44, IFIT2; journals.plos.org Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 5:09:02 PM
From: Thomas M.	Respond to of 361416

Ivermectin Mechanism #8 The second stage of Covid, the immunological stage, is the deadly one. Ivermectin reduces the excessive immune response (the cytokine storm). Upon sensing of coronaviruses by various pathogen recognition receptors, transcription factors nuclear factor kB (NF-kB) and interferon regulatory factor 3 and 7 (IRF3, IRF7) stimulate the production of pro-inflammatory cytokines and type I and III interferons (IFNs), respectively. sciencedirect.com Ivermectin improved mouse survival rate induced by a lethal dose of LPS. In addition, ivermectin significantly decreased the production of TNF-a, IL-1ß and IL-6 in vivo and in vitro. Furthermore, ivermectin suppressed NF-kB translocation induced by LPS. The results indicate that ivermectin may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kB pathway and improve LPS-induced survival in mice. This finding might provide a new strategy for the treatment of endotoxemia and associated inflammation. link.springer.com Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 6:09:33 PM
From: Thomas M.	1 Recommendation Recommended By i-node Read Replies (1) \| Respond to of 361416

Ivermectin Mechanism #9 NF-kB as part of cytokine production: The transcription factor NF-kB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-kB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. nature.com Ivermectin blocks the NF-kB pathway: Our results indicated that ivermectin at its very low dose, which did not induce obvious cytotoxicity, drastically reversed the resistance of the tumor cells to the chemotherapeutic drugs both in vitro and in vivo. Mechanistically, ivermectin reversed the resistance mainly by reducing the expression of P-glycoprotein (P-gp) via inhibiting the epidermal growth factor receptor (EGFR), not by directly inhibiting P-gp activity. Ivermectin bound with the extracellular domain of EGFR, which inhibited the activation of EGFR and its downstream signaling cascade ERK/Akt/NF-kB. The inhibition of the transcriptional factor NF-kB led to the reduced P-gp transcription. pubmed.ncbi.nlm.nih.gov Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 7:56:00 PM
From: Thomas M.	Respond to of 361416

Ivermectin Mechanism #10 STAT3 acts as a “central hub” that leads to the cytokine storm: We hypothesize that COVID-19 disease is due in large part to the actions of the SARS-CoV-2 NSP1 and ORF6 proteins, which cripple STAT1 function and predominantly promote STAT3 activation. STAT3 in turn upregulates PAI-1, and together these molecules serve as a central hub of reactions that perpetuate a catastrophic cascade. Our understanding of immune responses, coupled with lessons from SARS-CoV-1 and recent research on SARS-CoV-2, point to STAT1 and STAT3 as enticing drug targets because they function upstream of the cytokine storm and thrombosis. Developing vaccines will take some time, and attacking the downstream cytokine storm is difficult due to its many targets. Hence, in the short term, the manipulation of STAT1 and/or STAT3 may be the most practical strategy for treating COVID-19. nature.com Ivermectin inhibits STAT3: Ivermectin inhibits p21 activated kinase 1 (PAK1), a serine/threonine kinase with oncogenic activity, which then compromises STAT3 activity. In this case, ivermectin suppresses Akt/mTOR signaling by promoting the ubiquitination-mediated degradation of PAK1. In addition, PAK1 physically binds to both JAK1 and STAT3, and the resultant PAK1/STAT3 complex activates IL-6 gene transcription. When ivermectin inhibits JAK/STAT3 signaling by promoting PAK1 degradation, STAT3 activity is compromised and IL-6 production is decreased. Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 9:01:53 PM
From: Thomas M.	Read Replies (1) \| Respond to of 361416

Ivermectin Mechanism #11 PAK1 binds to STAT-3 and the resultant complex activates IL-6 which is responsible for cytokine storm: The PAK1-Stat3 Signaling Pathway Activates IL-6 Gene Transcription PAK1 interacts with signal transducer and activator of transcription 3 (Stat3), and PAK1 and Stat3 colocalize in the nucleus. the PAK1/Stat3 complex binds to the IL-6 promoter and regulates the transcription of the IL-6 gene. Inhibition of PAK1 and JAK2 in mammospheres reduces the nuclear pStat3 and extracellular IL-6 levels. mdpi.com Ivermectin inhibits PAK1: Our data showed that ivermectin could markedly decrease the expression of PAK1 Ivermectin downregulated PAK1 protein levels by targeting the lysine residues at K11, K29, K39, or K148 and promoting ubiquitination-mediated degradation. These results support ivermectin as a potent agent in the induction of ubiquitination-mediated degradation of PAK1 cancerres.aacrjournals.org Tom

To: J_F_Shepard who wrote (225105)	2/7/2022 10:35:56 PM
From: Thomas M.	Read Replies (2) \| Respond to of 361416

Ivermectin Mechanism #12 Ivermectin suppresses IL-6 and TNFa production, two major components of the cytokine storm: IVM dramatically reduces the Il-6/Il-10 ratio in lung tissue embopress.org ivermectin significantly decreased the production of TNF-a, IL-1ß and IL-6 in vivo and in vitro. link.springer.com Tom

To: J_F_Shepard who wrote (225105)	2/8/2022 1:28:44 AM
From: Thomas M.	Respond to of 361416

Ivermectin Mechanism #13 The spike protein binds to red blood cells and causes clumping, which can lead to clotting: SARS-CoV-2 spike protein and that this spike protein binds to the CD147 transmembrane receptor as well as to ACE2. The abundant distribution of CD147 on red blood cells (RBCs) suggests a hypothesized “catch” and “clump” framework whereby virally-mediated bindings of RBCs to other RBCs, platelets, white blood cells and capillary walls impede blood flow, which in turn may underlie key morbidities of COVID-19. papers.ssrn.com Ivermectin binds to the spike protein (preventing the spike from binding to red blood cells): Ivermectin docked in the region of leucine 91 of the spike ncbi.nlm.nih.gov Tom

To: J_F_Shepard who wrote (225105)	2/8/2022 1:42:12 AM
From: Thomas M.	Read Replies (1) \| Respond to of 361416

Ivermectin Mechanism #14 Covid causes heart damage: Reports suggest that the Middle East respiratory syndrome-related coronavirus (MERS-CoV) can cause acute myocarditis and heart failure. SARS-CoV-2 and MERS-CoV have similar pathogenicity, and the myocardial damage caused by infection with these viruses undoubtedly increases the difficulty and complexity of patient treatment. Myocardial injury associated with the SARS-CoV-2 occurred in 5 of the first 41 patients diagnosed with COVID-19 in Wuhan nature.com Ivermectin prevents heart damage by maintaining mitochondrial ATP levels when oxygen is low: Impaired mitochondrial ATP production in cardiomyocytes is one of the major causes of heart failure. A drug that maintains ATP production would, therefore, be an attractive heart failure treatment option. We performed high-throughput image-based screens under hypoxia, and identified mitochondrial ATP protectors, including the anti-parasite drug, ivermectin. We show that ivermectin increased mitochondrial ATP production by inducing Cox6a2 expression and inhibited the hypertrophic response of human iPSC-derived cardiomyocytes. Pharmacological inhibition of importin ß, a target of ivermectin, exhibited similar protective effects. Our studies indicate that compounds maintaining mitochondrial ATP under hypoxia may prevent pathological hypertrophy and improve cardiac function. thelancet.com Tom

To: J_F_Shepard who wrote (225105)	2/8/2022 1:52:21 AM
From: i-node	Respond to of 361416

>> FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problemsFDA Drug Safety Podcast Yes, it can cause a funny heartbeat, which usually stops as soon as you quit taking it. People seldom die of it. If you'd like to know more, this gives you further information. As you can see just about anything CAN cause it if you are at elevated risk. Certain medications can cause LQTS, but tends to affect who are already have a tendency. The medications may include:AntibioticsAntihistaminesAntidepressantsAntipsychoticsDiureticsOther causes may include electrolyte abnormalities such as:Low potassium levelsLow calcium levelsLow magnesium levelsRisk factors include:Family historyHeart diseaseGender: Women are at higher risk than menExcessive diarhea or vomiting - which causes imbalance in electrolytes