Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms

Author(s):  
Etheresia Pretorius ◽  
Chantelle Venter ◽  
Gert Laubshder ◽  
Maritha Kotze ◽  
Kelebogile Moremi ◽  
...  

Abstract We recognise that fibrin(ogen) amyloid microclots and platelet hyperactivation, that we have previously observed in COVID-19 and Long COVID/Post-Acute Sequelae of COVID-19 (PASC) patients, might form a suitable set of foci for the clinical treatment of the symptoms of long COVID/PASC. We first report on the comorbidities and symptoms found in a cohort of 845 South African Long COVID/PASC patients who filled in the South African Long COVID/PASC registry, of which hypertension and high cholesterol levels (dyslipidaemia) were the most important comorbidities. The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. This suggests that our sample was not at all atypical. Using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we analysed blood samples from 70 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases; these were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19. A subset of 24 patients was treated with one month of dual antiplatelet therapy (DAPT) (Clopidogrel 75mg/Aspirin 75mg) once a day, as well as a direct oral anticoagulant (DOAC) (Apixiban) 5 mg twice a day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day was also prescribed for gastric protection. Such a regime must only be followed under strict and qualified medical guidance to obviate any dangers, especially haemorrhagic bleeding, and of the therapy as a whole. Thromboelastography (TEG®) was used to assist in determining their clotting status. Each of the 24 treated cases reported that their main symptoms were resolved and fatigue as the main symptom was relieved, and this was also reflected in a decrease of both the fibrin amyloid microclots and platelet pathology scores. Nine patients were genotyped for genetic variation in homocysteine metabolism implicated in hypertension, a common COVID-19 co-morbidity reported in both patients found to be homozygous for the risk-associated MTHFR 677 T-allele. Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. The removal and reversal of these underlying epitheliopathies underlying this provide an important treatment option that seems to be highly efficacious, and warrants controlled clinical studies.

2011 ◽  
Vol 301 (6) ◽  
pp. G1031-G1043 ◽  
Author(s):  
Yoshihiro Kamada ◽  
Shinichi Kiso ◽  
Yuichi Yoshida ◽  
Norihiro Chatani ◽  
Takashi Kizu ◽  
...  

Recent studies indicate an accelerated progression of nonalcoholic steatohepatitis (NASH) in postmenopausal women. Hypercholesterolemia, an important risk factor for NASH progression, is often observed after menopause. This study examined the effects of estrogen on NASH in ovariectomized (OVX) mice fed a high-fat and high-cholesterol (HFHC) diet. To investigate the effects of estrogen deficiency, OVX mice and sham-operated (SO) mice were fed normal chow or HFHC diet for 6 wk. Next, to investigate the effects of exogenous estrogen replenishment, OVX mice fed with HFHC diet were treated with implanted hormone release pellets (containing 17β-estradiol or placebo vehicle) for 6 wk. OVX mice on the HFHC diet showed enhanced liver injury with increased liver macrophage infiltration and elevated serum cholesterol levels compared with SO-HFHC mice. Hepatocyte monocyte chemoattractant protein-1 (MCP1) protein expression in OVX-HFHC mice was also enhanced compared with SO-HFHC mice. In addition, hepatic inflammatory gene expressions, including monocytes chemokine (C-C motif) receptor 2 (CCR2), were significantly elevated in OVX-HFHC mice. Estrogen treatment improved serum cholesterol levels, liver injury, macrophage infiltration, and inflammatory gene expressions in OVX-HFHC mice. Moreover, the elevated expression of liver CCR2 and MCP1 were decreased by estrogen treatment in OVX-HFHC mice, whereas low-density lipoprotein dose dependently enhanced CCR2 expression in THP1 monocytes. Our study demonstrated that estrogen deficiency accelerated NASH progression in OVX mice fed HFHC diet and that this effect was improved by estrogen therapy. Hypercholesterolemia in postmenopausal women would be a potential risk factor for NASH progression.


PEDIATRICS ◽  
1991 ◽  
Vol 88 (2) ◽  
pp. 250-258
Author(s):  
David C. Goff ◽  
Ge A. Donker ◽  
Darwin R. Labarthe ◽  
Jesse D. Ragan ◽  
A. Thomas Adkins ◽  
...  

Four pediatricians introduced a portable cholesterol analyzer into their group practice. Their experience is described on the basis of 12 months of screening in 1665 children and adolescents. The overall 50th and 90th percentile values for a subgroup of 1406 routinely screened children were 156 and 197 mg/dL, respectively, but there was marked variation in these values among specific age and sex groups. Cholesterol levels decreased by age group during the early teenage years and increased thereafter, these changes occurring at ages approximately 2 years younger for girls than for boys. Further analysis of screening results for 398 sibling pairs demonstrated significant concordance between paired cholesterol levels when classified by the respective age- and sex-specific 90th percentile values for each member of the pair. Sibling pairs in which both members' cholesterol values exceeded their 90th percentile value were identified 2.4 times as frequently as expected (confidence interval 1.1 to 4.5, P = .029). The observations reported here indicate that office-based cholesterol screening in a pediatric practice may be both practical and useful, although further consideration of screening criteria is needed. Age- and sex-specific reference values for cholesterol levels during childhood could improve screening results. Special emphasis should be directed toward screening siblings of children in whom high cholesterol levels have been detected.


1998 ◽  
Vol 42 (12) ◽  
pp. 3146-3152 ◽  
Author(s):  
Kishor M. Wasan ◽  
Allison L. Kennedy ◽  
Shawn M. Cassidy ◽  
Manisha Ramaswamy ◽  
Lorilynne Holtorf ◽  
...  

ABSTRACT The purpose of this study was to determine if a relationship exists among total serum and lipoprotein cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the serum pharmacokinetics of AmpB in hypercholesterolemic rabbits administered AmpB and AmpB lipid complex (ABLC). After 10 days of cholesterol-enriched diet (0.50% [wt/vol]) or regular rabbit diet (control), each rabbit was administered a single intravenous bolus of AmpB or ABLC (1.0 mg/kg of body weight). Blood samples were obtained before administration and serially thereafter for the assessment of serum pharmacokinetics, kidney toxicity, and serum lipoprotein distribution. Rabbits were humanely sacrificed after all blood samples were obtained, and tissues were harvested for drug analysis. Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total serum cholesterol and low-density lipoprotein (LDL) cholesterol levels compared with levels in rabbits on a regular diet. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered AmpB. However, the magnitude of this increase was 2.5-fold greater in cholesterol-fed rabbits than in regular diet-fed rabbits. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered ABLC. Whereas AmpB pharmacokinetics were significantly altered in cholesterol-fed rabbits administered free AmpB, similar AmpB pharmacokinetics were observed in both rabbit groups administered ABLC. Renal AmpB levels were significantly increased in cholesterol-fed rabbits administered AmpB compared with those in all other groups. Hepatic and lung AmpB levels were elevated in cholesterol-fed rabbits administered free AmpB compared to controls. In addition, hepatic, lung, and spleen AmpB levels were significantly decreased in cholesterol-fed rabbits administered ABLC compared to controls. An increased percentage of AmpB was recovered in LDL–very-low-density lipoprotein fraction when free AmpB was administered to cholesterol-fed rabbits compared with those in all other groups. These findings suggest that increases in cholesterol, specifically, LDL cholesterol levels, modify the disposition and renal toxicity of free AmpB. However, the pharmacokinetics and renal toxicity of ABLC were independent of elevations in total and LDL cholesterol levels.


2021 ◽  
Vol 1 (1) ◽  
pp. 11-16
Author(s):  
Endah Prayekti ◽  
Ary Andini

Parties who become partners in community service activities are the village community of Sumbersono, Mojokerto Regency. Based on the 2017 health profile in Mojokerto District, there are 117,309 elderly people. The Mojokerto district government has a health program for the elderly, namely the Elderly Health Service (Usila). Usila is a health service according to the standards in the elderly guidelines in a health facility in one work area and time period. Examination of the elderly programmed by the Mojokerto district government has been carried out at the Puskesmas that serves the elderly, but the elderly need more routine checks to monitor cholesterol levels. Another thing that is a problem is the relatively expensive cholesterol examination so that there are limitations in the self-examination by the community. Cholesterol examination methods for community service were using POCT and interviews related to health complaints from community service participants. There were 44 community service participants, not only from the elderly but from middle age. Of the 27 elderly, 10 elderly have normal cholesterol levels while 17 elderly have high and very high of cholesterol levels. Of the 17 middle age participants, 7 of them had normal cholesterol levels and 10 people had high and very high cholesterol levels. The interviews showed that almost all participants had health complaints that resembled complaints due to high cholesterol level. It is recommended to perform other health examination and not be limited to the elderly.


2021 ◽  
Vol 4 (2) ◽  
pp. 80-85
Author(s):  
Irpan Ali Rahman ◽  
Endrian Mulyadi Justitia Waluyo ◽  
Shafira Aisyah Darmawan

Hypertension is an increase in systolic blood pressure above 140 mmHg and diastolic blood pressure above 90 mmHg. The number of hypertension sufferers has increased each year, in 2015 it reached 19,552, in 2016 it reached 24,750 and in 2017 it reached 38,057. In 2017 there were 115 hypertensive patients recorded in the report book that checked their health at the Sadananya Health Center. One of the causes of the high incidence of hypertension is cholesterol caused by the consumption of inappropriate food. One of the laboratory examinations to support hypertension diagnosis is blood cholesterol examination which can show excess cholesterol which makes hypertension difficult to control. To know the description of total cholesterol levels in hypertensive patients at the Sadananya Health Center. Quantitative descriptive, the population in this study were people with hypertension at the Sadananya Health Center. Sampling with accidental sampling, as many as 30 respondents. The cholesterol examination method used is CHOD-PAP. The results showed that blood pressure in respondents all had high blood pressure, namely >140/90 mmHg (100%), a high cholesterol level of 24 respondents (80%), blood pressure 140-150 who had high cholesterol as many 13 respondents, blood pressure 160-170 who had high cholesterol as much 6 respondents, blood pressure >180 who had high cholesterol as much 5 respondents. This study concludes that hypertensive clients have more high total cholesterol levels, which is as much as 80% and normal 20%. More hypertensive patients have high total cholesterol levels, which are 80% and 20% normal.


Jurnal Biota ◽  
2017 ◽  
Vol 3 (2) ◽  
pp. 71
Author(s):  
Muhammad Sungging Pradana ◽  
Imam Suryanto

Cholesterol is a waxy substance which is mainly made in the body. Cholesterol can provide benefits. However, having too much cholesterol in the blood can increase risk of cardiovascular disease. Prevention and treatment of cardiovascular disease can be done by taking synthetic drugs such as statin. Due to side effects of synthetic drugs, it is necessary to substitute synthetic drugs with herbal plant and some natural component in these plants. The important ones is garlic. Garlic contain organosulphur compounds such as diallyldisulphide (DADS), dipropyldisulphide (DPDS), diallytrisulphide (DATS) and dipropyltrisulphide (DPTS) which have anti artherogenic effects. Garlic also have active agent allicin, can reduce the levels of cholesterol. This research was conducted at the Experimental Animal Enclosure Installation, Center for Veterinary Farma Surabaya with 3 experimental groups. Animals used in this research were female mice 2 months old were feeding with high cholesterol feed such as fried offal of chicken twice a day as much 0,5 cc/ day every 3 days. On the 3rd day, the levels of cholesterol in each group was examined. On the 4th day, mice in group 3 were given 1cc of garlic juice. 1 hour later mice was examined blood cholesterol using Strip Test Easy Touch GCU. The results through T-paired test on SPSS stated that (p < 0,05), it means there is influence between the 3 treatment of mice. This results it can be concluded that the provision of garlic juice can reduced blood cholesterol levels in mice after fed with high cholesterol.


2001 ◽  
Vol 85 (02) ◽  
pp. 221-225 ◽  
Author(s):  
Anetta Undas ◽  
Robert Undas ◽  
Jan Brożek ◽  
Andrzej Szczeklik ◽  
Jacek Musiał

SummaryAspirin and statins are beneficial in coronary heart disease across a broad range of cholesterol levels. We assessed the effects of low-dose aspirin (75 mg daily) on thrombin generation in patients with coronary heart disease and average blood cholesterol levels. We also investigated whether in patients with borderline-high cholesterol level who have been already taking aspirin, additional treatment with simvastatin would affect thrombin generation.Seven-day treatment with low-dose aspirin decreased thrombin generation ex vivo only in patients with total cholesterol 5.2 mmol/L. In patients with higher cholesterol levels aspirin had no effect. In these patients, already taking low-dose aspirin, additional three-month simvastatin treatment resulted in a reduction of thrombin generation. This demonstrates that low-dose aspirin depresses thrombin generation only in subjects with desirable blood cholesterol levels, while in others, with borderline-high cholesterol, thrombin formation is being reduced following the addition of simvastatin.


2019 ◽  
Vol 19 (5) ◽  
pp. 375-383
Author(s):  
Marco Bertolotti ◽  
Giulia Lancellotti ◽  
Chiara Mussi

2003 ◽  
Vol 9 (1) ◽  
pp. 5 ◽  
Author(s):  
Sandra Brink ◽  
Piet Oosthuizen ◽  
Robin Emsley ◽  
Irene Mbanga ◽  
Natasha Keyter

Background. Co-morbidity between substance abuse and psy- chotic disorders is high. Few studies have examined therelationship between first-episode psychosis and substance abuse. Several questions emerge from this common relationship and many of them remain unanswered.Objectives. To determine the effect of substance abuse on psychosis in terms of onset, duration, severity of symptoms, use of medication and outcome.Method. Thirty - three subjects with first-episode psychosis, as well as primary caregivers, were interviewed re g a rding substance abuse and its relation to illness. Thirty-six control subjects were also interv i e w e d .Results. Twenty-seven per cent of subjects abused substances in the 3 months before onset of illness, and 77.8% of the abusers w e re male. Subjects in the first-episode psychosis group were m o re likely to choose cannabis as their substance of abuse than c o n t rols. They also started abusing substances at a younger age than controls. Subjects with first-episode psychosis who abused substances presented at an earlier age than non-abusers. Substances affected symptoms at baseline presentation .Conclusions. Substance abuse has a significant impact on first- onset psychosis as far as age of onset and symptom severity are c o n c e rned. Subjects with an underlying vulnerability to psychosis seem to start abusing substances at an earlier age than the general population. Males are more likely to abuse substances than females.


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