Medcram (Dr Seheult) covers Ivermectin again and discusses another methanism (preventing covid19 spike protein attachment to ACE2 and CD147 on red blood cells) that was proposed in the June 1 paper

stereomatch | 8 points | Jul 16 2020 07:30:21

Medcram (Dr Seheult) covers Ivermectin again and discusses another methanism (preventing covid19 spike protein attachment to ACE2 and CD147 on red blood cells) that was proposed in the June 1 paper

EDIT: title should have "mechanism" instead of "methanism"

Medcram (Dr Seheult) has previously discussed papers on ivermectin.

In latest video he discusses:

medcram #96 video

https://youtu.be/kk7KNBak-i0

RNA vaccines (Moderna RNA vaccine)
Ivermectin
von Willebrand factor and clotting

I will discuss the Ivermectin and von Willebrand sections here.

He is saying others starting to also suggest von willebrand factor

https://medicalxpress.com/news/2020-07-complications-covid-von-willebrand-factor.html Complications from COVID-19 may depend on von Willebrand factor in the blood July 6, 2020 , St. Petersburg State University

micro-thrombi in micro-vasculature leading to hypoxia without lung stiffness ..

6:30 - he wants to introduce another reason related to blood clots - ivermectin

ok seen this before:

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3636557 Ivermectin for COVID-19 Treatment: Clinical Response at Quasi-Threshold Doses Via Hypothesized Alleviation of CD147-Mediated Vascular Occlusion 1 Jul 2020 David Scheim US Public Health Service

He says here is a paper that suggests another mode of action for ivermectin

CD147 is a protein that on the red blood cell

RBCs are found in blood clots as well as thrombin and fibrin etc. (?)

CD147 is the entry point for malaria into red blood cell

CD147 is also considered by some to be a possible binding site for covid19 spike protein

so just like ACE2 receptors

however it doesn't help virus if they enter RBCs as there no nucleus in RBCs

and if no nucleus, then are there doesnt need to be ribosomes in RBCs since there is no protein synthesis occuring

if no protein synthesis occurring, RBCs are a kind of dead end

as virus cannot reproduce as RBCs lack the machinery for virus to reproduce ..

however theory goes that virus binds to CD147 and tends to make these cells sticky

and cause thrombosis .. and that's what this article suggests

article says there is such a behavior seen in malaria - as CD147 similarly does ..

saying ivermectin shields covid19 spike protein

and ivermectin prevents this from happening

(has ivermectin been studied for malaria ?)

also potentially prevents spike protein binding to ACE2 receptor

however huge number of CD147 - which article hypothesizes "catch and clump" framework

ie virally mediated binding of RBCs to other RBCs ..

(could this be the reason for widely reported "thicker blood" in covid19 patients, or is that due to von Willebrand factor etc. ?)

It is proposed that higher doses of IVM could yield sharply greater clinical benefits. In several clinical studies, IVM at doses of up to 2,000 µg/kg, ten times that used in the Florida study, were well tolerated. The potential for major dose-response gains is evaluated based upon studies indicating that IVM shields 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. The proposed catch and clump scenario for COVID-19 has a parallel in malaria, for which CD147 is central to the infectious process. The core morbidity of severe malaria is caused by similar clumps and adhesions to endothelium centering around infected RBCs. These underlie the much greater incidence of severe malaria for blood groups A or B vs. O, caused by adhesive RBC membrane trisaccharides associated with blood groups A and B. COVID-19 is likewise much more prevalent for blood groups A or B vs. O. More generally, hemagglutination, the formation of such RBC-pathogen clusters, is common for enveloped viruses. Under this hypothesized framework, a significantly higher rate of capillary flow in younger people could explain a corresponding decreased severity of COIVD-19. This proposed hypothesis and the associated potential for major IVM dose-response gains could be tested, for example, by monitoring blood flow in COVID-19 patients before and after IVM intake using nailfold capillaroscopy.

10:45 - previously we talked of ivermectin and how it impeded the nuclear transport system or transporting and converting viral proteins into the nucleus

this article is proposing a novel theory that ivermectin may be interfering with binding of virus spike protein to CD147 but also ACE2 receptors

then talks of this earlier nature review of ivermectin

https://www.nature.com/articles/s41429-020-0336-z 12 June 2020 Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen Fatemeh Heidary & Reza Gharebaghi

Ivermectin, owing to its antiviral activity, may play a pivotal role in several essential biological processes, therefore it could serve as a potential candidate in the treatment of different types of viruses including COVID-19. As noted, the activity of ivermectin in cell culture has not reproduced in mouse infection models against many of the viruses and has not been clinically proven either, in spite of ivermectin being available globally. This is likely related to the pharmacokinetics and therapeutic safety window for ivermectin. The blood levels of ivermectin at safe therapeutic doses are in the 20–80 ng/ml range [44], while the activity against SARS-CoV2 in cell culture is in the microgram range. Ivermectin is administered orally or topically. If safe formulations or analogs can be derived that can be administered to achieve therapeutic concentrations, ivermectin could be useful as a broad-spectrum antiviral agent.

[-] DZinni | 2 points | Jul 16 2020 17:16:35

Ivermectin has been studied for Malaria. I do not remember the exact results.

[-] stereomatch | 1 points | Jul 16 2020 17:57:25

Here is some info on ivermectin and malaria.

Evidently it has benefit as it kills the mosquito which tries to feed off a person taking ivermectin.

In addition the studies seem to suggest there may be a benefit in malaria disease outcome for the person taking ivermectin.

Commentary on a paper:

https://www.jwatch.org/na48726/2019/03/20/mass-administration-ivermectin-effective-against-malaria March 20, 2019 Mass Administration of Ivermectin: Effective Against Malaria Mary E. Wilson, MD reviewing Foy BD et al. Lancet 2019 Mar 13 Chaccour C and Rabinovich NR. Lancet 2019 Mar 13

In a trial in Burkina Faso, repeated mass ivermectin administration substantially reduced malaria cases among children. Oral ivermectin can kill mosquitoes that bite recipients of the drug (NEJM JW Infect Dis Jun 2018 and Lancet Infect Dis 2018; 18:P615). But can this agent effectively combat malaria? In a cluster-randomized trial in malaria-endemic Burkina Faso, investigators mass-administered an initial oral ivermectin dose (150–200 µg/kg) plus five additional doses every 3 weeks in four intervention villages; in four control villages, participants received only the initial dose. Cumulative malaria incidence in children aged ≤5 years was significantly lower in the intervention villages than the control villages (risk ratio, 0.8), and the proportion of children with no malaria episodes was more than twofold higher (20% vs. 9%). In a subgroup analysis, decreases in malaria were seen among children in intervention villages who had or had not received treatment, suggesting a community benefit from ivermectin. No increase in drug-related harms was observed with repeated treatment. COMMENT In addition to drug resistance, behavioral changes in mosquitoes allow them to evade the usual malaria control strategies; thus, providing ivermectin as an insecticide in the blood of humans has value as a complementary tool. Mass drug treatments — which usually exclude pregnant and breast-feeding women and anyone shorter than 90 cm (i.e., most children younger than 5 years) — reach about 75% of a village's population. Although this study was small, it shows that mass treatment with ivermectin can produce a measurable decrease in malaria in young children, the most vulnerable population. As editorialists note, additional trials are needed to assess ivermectin dosing, distribution, and safety — but they are optimistic that this approach may be useful against residual transmission. Slow-release formulations could eliminate the inconvenience of frequent dosing. The authors also raise the possibility that ivermectin has direct activity against malaria parasites in humans.

Above commentary refers to this paper:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32321-3/fulltext APRIL 13, 2019 Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial Prof Brian D Foy, PhD Haoues Alout, PhD Jonathan A Seaman, BSc Sangeeta Rao, PhD Tereza Magalhaes, PhD Martina Wade, BSc et al. March 13, 2019 DOI:https://doi.org/10.1016/S0140-6736(18)32321-3

https://www.isglobal.org/en_GB/-/nueva-evidencia-respalda-el-uso-de-ivermectina-como-una-herramienta-en-la-eliminacion-de-la-malaria New Evidence Supports the Use of Ivermectin as a Tool for Malaria Elimination The mosquito-killing drug shows effect for one month according to a study performed in Kenya 28.03.2018

A clinical trial published in Lancet Infectious Diseases shows that multiple, high doses of ivermectin are well tolerated and able to kill mosquitoes feeding on humans for up to one month after treatment. In a linked Comment, Regina Rabinovich, from the Harvard TH Chan School of Public Health and director of the Malaria Elimination Initiative at ISGlobal – center supported by the “la Caixa” Foundation- says “this study sets the stage for progress in the development and evaluation of ivermectin for vector control”. The study was funded by the Malaria Elimination Scientific Alliance (MESA), with headquarters in ISGlobal.
In a trial conducted at Kisumu, Kenya, and led by the Liverpool School of Tropical Medicine, researchers tested the safety and efficacy (in terms of mosquito-killing capacity) of higher doses of ivermectin. They treated 141 adults with uncomplicated malaria with the antimalarial treatment plus either 3 days of ivermectin (600 or 300 µg/kg per day) or placebo. Results show that the blood of patients treated with both ivermectin doses induced high mosquito mortality, even 28 days after treatment. Modelling analysis suggests that adding the 300 µg/kg dose of ivermectin to mass antimalarial drug administration could significantly reduce malaria prevalence by an additional 44% in low transmission settings aiming at malaria elimination. In her comment, Rabinovich underlines that “given the high variability of the vector and the parasite, it will likely take more than one approach to confront the challenge of malaria elimination. Ivermectin would provide a short-term option, while new endectocides with improved characteristics like longer duration of action are developed.”

Reference

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30163-4/fulltext Menno R Smit, Eric O Ochomo, Ghaith Aljayyoussi, et al. Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial. 27 March 2018 https://doi.org/10.1016/S1473-3099(18)30163-4

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30176-2/fulltext Regina Rabinovich. Ivermectin: repurposing an old drug to complement malaria vector control. 27 March 2018 https://doi.org/10.1016/S1473-3099(18)30176-2.

examining the papers:

However, standard, single doses of 150–200 μg/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 μg/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment.

... to receive 3 days of ivermectin 300 μg/kg per day, ivermectin 600 μg/kg per day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine.

Findings Between July 20, 2015, and May 7, 2016, 741 adults with malaria were assessed for eligibility, of whom 141 were randomly assigned to receive ivermectin 600 μg/kg per day (n=47), ivermectin 300 μg/kg per day (n=48), or placebo (n=46). 128 patients (91%) attended the primary outcome visit 7 days post treatment. Compared with placebo, ivermectin was associated with higher 14 day post-feeding mosquito mortality when fed on blood taken 7 days post treatment (ivermectin 600 μg/kg per day risk ratio [RR] 2·26, 95% CI 1·93–2·65, p<0·0001; hazard ratio [HR] 6·32, 4·61–8·67, p<0·0001; ivermectin 300 μg/kg per day RR 2·18, 1·86–2·57, p<0·0001; HR 4·21, 3·06–5·79, p<0·0001). Mosquito mortality remained significantly increased 28 days post treatment (ivermectin 600 μg/kg per day RR 1·23, 1·01–1·50, p=0·0374; and ivermectin 300 μg/kg per day 1·21, 1·01–1·44, p=0·0337). Five (11%) of 45 patients receiving ivermectin 600 μg/kg per day, two (4%) of 48 patients receiving ivermectin 300 μg/kg per day, and none of 46 patients receiving placebo had one or more treatment-related adverse events.

so had some adverse events ?

Ivermectin at both doses assessed was well tolerated and reduced mosquito survival for at least 28 days after treatment. Ivermectin 300 μg/kg per day for 3 days provided a good balance between efficacy and tolerability, and this drug shows promise as a potential new tool for malaria elimination.

300mcg/kg x 80kg person = 24mg ie 6mg x 4 tablets

https://blogs.biomedcentral.com/bugbitten/2020/01/28/ivermectin-inhibiting-transmission-of-the-malaria-parasite-beyond-insecticidal-activity/ Ivermectin: inhibiting transmission of the malaria parasite beyond insecticidal activity Blocking the Plasmodium life cycle can be achieved through the use of insecticides, or by strategies aimed at preventing the parasite from developing inside its mosquito vector, a multi-step process known as sporogony. But what if both could be done at the same time?

António M. Mendes, Raquel Azevedo and Miguel Prudêncio 28 Jan 2020

[-] converter-bot | 1 points | Jul 16 2020 17:57:39

90 cm is 35.43 inches

[-] stereomatch | 1 points | Jul 16 2020 17:58:31

https://www.infectiousdiseaseadvisor.com/home/topics/vector-borne-illnesses/ivermectin-may-be-a-promising-preventive-intervention-for-malaria/ April 3, 2019 Frequent, Repeated Mass Ivermectin Administration Reduces Malaria Transmission

Of the 327 children in the intervention group, 69 were treatment with ivermectin 4 to 6 times. In the control group, 52 of 263 children were treated once with ivermectin. When accounting for this confounder, there was a 44% lower incidence in the intervention group. The percentage of children with no malaria episodes in the intervention group was more than twice that in the control group (20% vs 9%, respectively). Moreover, the median time to first malaria episode was longer in the intervention group than in the control group.

“Supporting these data, ivermectin-treated children from the intervention group had a significantly reduced molecular force of infection compared with those from the control group, indicating that such repeated treatments affect malaria incidence connected to P falciparum clonal exposure or development,” noted the researchers. Future research will need to verify the observations made in this study, as well as the safety and efficacy of higher dose7 or slow-release formulations.