Paradoxical Thrombotic Effects of Aspirin: Experimental Study on 1000 Animals

Doutremépuich, Christian; Aguejouf, Omar; Desplat, Vanessa; Eizayaga, Francisco Xavier

doi:10.2174/187152910791292510

Cited by 13 publications

(13 citation statements)

References 23 publications

(25 reference statements)

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“…Unpublished analysis of previously published data. 15,19 less selectively than NS-398. In the case of ASA, the proposed mechanism is that the primary effect (100 mg/kg) is produced by COX-1 inhibition, decreasing TXA 2 in the platelets.…”

Section: Discussionmentioning

confidence: 77%

“…When analysing previously published raw data, 15,19 the primary effect of COX inhibition is as follows: COX-1 selective inhibition decreases the number of emboli; COX-2 selective inhibition increases the number of emboli; indomethacin decreases the number of emboli; and SC-560 plus NS-398 together decrease the number of emboli (►Fig. 9).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to these groups, separate groups were formed with simultaneous inhibition of COX-1 and COX-2 at 10 mg/kg b.w., with ASA in different doses (100 mg/kg b.w, 1 mg/kg b.w., 5 cH, 9 cH and 15 cH). 15 The realisation of this extended study took more than 1 year for the laser investigation plus statistical analysis. As a result of this crossed dose-response study, the higher doses of ASA (100 mg/kg and 1 mg/kg) decreased thrombosis in a significant way, while the lower ones (9 cH and 15 cH) increased thrombosis when compared to control.…”

Section: Effect Of Aspirin After Non-selective and Selective Inhibitimentioning

confidence: 99%

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Effects of Ultra-Low-Dose Aspirin in Thrombosis and Haemorrhage

Eizayaga

Belon²,

Desplat

et al. 2019

Homeopathy

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Background Aspirin is the oldest and possibly the most widely used pharmacologically active substance still used in allopathic medicine. Its effect on fever and inflammation has paved the way to its anti-thrombotic effect. Dilutions of aspirin have been tested for many years in the University of Bordeaux, in humans as well as in animal models. Methods This article is a review of the totality of articles published by the Laboratory of Hematology of the Faculty of Pharmacy of the University of Bordeaux, reporting different doses and dilutions of aspirin, different kinds of inhibitors, transgenic mice and animal models of disease such as portal hypertension and cirrhosis. Results Homeopathic dilutions of aspirin, notably 15 cH, have shown a pro-thrombotic effect in humans and in in-vivo animal studies. Longitudinal studies in rats have also shown an initial anti-thrombotic effect followed by a pro-thrombotic effect of aspirin several days after a single high-dose administration. This pro-thrombotic effect seems to act by inhibiting the cyclooxygenase (COX)-2 pathway in studies performed with COX selective inhibitors and in knock-out mice without COX-1 or COX-2. This effect may explain the thrombo-embolic complications described after aspirin withdrawal for the purposes of surgery or after non-compliance with anti-platelet therapy, and it may be beneficial in normalising primary haemostasis and decreasing haemorrhage in animal models of portal hypertension and cirrhosis. Conclusions Aspirin 15 cH acts through the inhibition of the COX-2 pathway producing a clear pro-thrombotic effect. Further studies should clarify if the pro-thrombotic effect of aspirin withdrawal and the effect of aspirin 15 cH are related, as secondary effects of the same drug. Clarifying this last outcome may be of great significance to public health.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Aspirin After Non-selective and Selective Inhibitimentioning

confidence: 99%

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Effects of Ultra-Low-Dose Aspirin in Thrombosis and Haemorrhage

Eizayaga

Belon²,

Desplat

et al. 2019

Homeopathy

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“…Attempts to explain the mechanism of the biological effect of physical and chemical factors in the ULD [17][18][19][20][21] have not led to a single opinion to date. Nevertheless, ULD in a number of cases found a successful application in medicine [22][23][24] and veterinary medicine [25,26].…”

mentioning

confidence: 99%

Ultra-Low Concentrations of Benzimidazole Derivatives Can Increase Bull and Horse Semen Resistance at Cryopreservation and Under the Influence of Damaging Factors

Nikitkina¹,

Shapiev²,

Plemyashov³

et al. 2017

S-h. biol.

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A b s t r a c tOne of the possible ways to improve sperm cryopreservation is to find how to increase the resistance to damaging effects of low temperatures. Here we summarize our findings on the bull and stallion semen cryoresistance as influenced by ultra-low concentrations of biologically active substances, the ethyl-1-benzimidazol-2-yl-sulfanyl, 2-ethylsulfanyl-benzimidazol-1-yl and 2-benzimidazol-1-yl-acetic acid. It was found that these substances increased survivability of bull semen during storage in lactose-citrate semen extender. The best motility and vitality of sperm after freezing and thawing was observed when sperm was diluted by extender with added 2-benzimidazol-1-yl-acetic acid in the ultra-low concentrations of 10  13 to 10  15 M. The viability of sperm to 10 % motility was 73 % higher as compared to control. Similarly, freezing equine sperm in extender supplemented with 2-benzoimidazol-1-yl-acetic acid at 10  13 M was more effective: the semen survival after freezing and thawing was 8.1 % (P < 0.01) higher than that in the control, and the intactness of acrosome was 1.9±0.63 % higher (P < 0.05). 2-Benzimidazol-1-ylacetic acids also improved semen vitality at 40 С when different osmolarity and after cold shock. It can be assumed that the observed phenomenon is likely due to the protective effect of 2-benzimidazole-1-yl-1-acetic acid to plasma membrane and the mitochondria membrane structure of spermatozoa. Study of respiration in bovine sperm after freezing and thawing confirmed this assumption. Indeed, dinitrophenol almost equally increased cell respiration despite the presence or absence of 2-benzimidazole-1-yl-1-acetic acid in the semen extender while succinate, which penetrates through the damaged membranes, had less stimulating effect when 2-benzimidazole-1-yl-1-acetic acid added. The studies suggested the hypothesis that benzimidazole, a biologically active substance, at ultra-low concentrations can bind to a receptor on the sperm outer membrane resulting in the cell membrane restructuring. At the same time, the changes in viscosity of water associated with the membrane proteins may occur due to hydrogen bonds between water molecules and acid residues of benzimidazole molecules. As a result stability of the membrane structures to damaging effect of varying osmotic pressure increases. Possibly crystal formation of water associated with the cell membranes is decreasing during freezing that also reduces the damaging effect.Keywords: sperm, freezing, benzimidazole, ultralow concentrations, cell membrane, mitochondria, bulls, stallions Despite widespread use of cryopreserved sperm in breeding various types of farm animals, the death of up to 40-50 % of germ cells after freezing remains a problem for the practice of artificial insemination, so the search for ways to make spermatozoa resistant to the damaging effect of low temperatures is still relevant [1][2][3][4][5].Nonspecific increase in cell resistance under the influence of chemicals of different nature in subthreshold doses and concen...

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“…Попытки объяснить механизм биологического действия физических и химических факторов в СМД (17)(18)(19)(20)(21) к настоящему времени не привели к единому мнению. Тем не менее, СМД в ряде случаев нашли успешное применение в медицине (22)(23)(24) и ветеринарии (25,26).…”

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Сверхмалые Концентрации Производных Бензимидазола Повышают Устойчивость Сперматозоидов Быков И Жеребцов При Криоконсервации И Действии Вредных Факторов

Nikitkina¹,

Shapiev²,

Племяшов³

et al. 2017

S-h. biol.

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Один из подходов к решению практических проблем криоконсервации клеток заключается в повышении устойчивости сперматозоидов к повреждающему действию низких температур. Мы изучили влияние производных бензимидазола этил-1-бензимидазол-2-ил-сульфанила, 2-этилсульфанилбензимидазол-1-ила и 2-бензимидазол-1-ил-1-уксусной кислоты в концентрациях 10  3 , 10  5 , 10  11 , 10  13 , 10  15 М на сохранность сперматозоидов при замораживании и оттаивании, на их устойчивость к холодовому шоку и изменению осмотического давления. Установлено, что изученные вещества повышали живучесть бычьих сперматозоидов при хранении в лактозо-цитратной среде. При этом наибольшую активность и сохранность отмечали при введении в среду для замораживания спермы 2-бензимидазол-1-ил-1-уксусной кислоты в сверхнизкой концентрации 10  13-10  15 М. Время переживания сперматозоидов до сохранения подвижности у 10 % клеток повышалось по сравнению с контролем на 73 %. Аналогичные результаты получили при замораживании-оттаивании спермы жеребцов в присутствии 2-бензимидазол-1-ил-1-уксусной кислоты в концентрации 10  13 М: доля подвижных неповрежденных клеток после замораживания-оттаивания оказалась на 15,2±3,49 млн/мл (Р < 0,01) больше, чем в среде без добавки. Выживаемость сперматозоидов быков после замораживания-оттаивания была на 8,1 % (Р < 0,01) выше, чем в контроле, сохранность акросом-на 1,9±0,63 % (Р < 0,05) выше. При изменении осмолярности среды для разбавления спермы и после холодового шока 2-бензимидазол-1-ил-1-уксусная кислота увеличивала живучесть сперматозоидов быка при повышенной температуре (40 С). Можно предположить, что наблюдаемый эффект связан с защитным действием 2-бензимидазол-1-ил-1-уксусной кислоты на плазматическую мембрану и мембранные структуры митохондрий сперматозоидов. Действительно, динитрофенол практически одинаково усиливал клеточное дыхание в опыте и контроле, тогда как сукцинат, который проникает через поврежденные мембраны, оказывал меньшее стимулирующее влияние в присутствии 2-бензимидазол-1-ил-1-уксусной кислоты. В результате проведенных исследований предложена гипотеза о механизме действия сверхмалых концентраций производных бензимидазола на криорезистентность половых клеток при замораживании. Молекулы исследуемого вещества взаимодействуют с рецептором на внешней мембране сперматозоида, что взывает перестройку мембранных структур клетки. Одновременно происходит изменение вязкости воды, ассоциированной с белками мембраны, из-за формирования водородных связей с кислотными остатками в молекуле производного бензимидазола. В результате повышается устойчивость мембранных структур сперматозоидов к повреждениям вследствие колебаний осмотического давления. Такое состояние воды, возможно, сказывается на характере кристаллообразования при замерзании в сторону уменьшения размеров кристаллов, что снижает их повреждающее действие.

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Paradoxical Thrombotic Effects of Aspirin: Experimental Study on 1000 Animals

Cited by 13 publications

References 23 publications

Effects of Ultra-Low-Dose Aspirin in Thrombosis and Haemorrhage

Effects of Ultra-Low-Dose Aspirin in Thrombosis and Haemorrhage

Ultra-Low Concentrations of Benzimidazole Derivatives Can Increase Bull and Horse Semen Resistance at Cryopreservation and Under the Influence of Damaging Factors

Сверхмалые Концентрации Производных Бензимидазола Повышают Устойчивость Сперматозоидов Быков И Жеребцов При Криоконсервации И Действии Вредных Факторов

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