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Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 143
Author(s):  
Synne S. Hansen ◽  
Tina M. Pedersen ◽  
Julie Marin ◽  
Neoma T. Boardman ◽  
Ajay M. Shah ◽  
...  

The present study aimed to examine the effects of low doses of angiotensin II (AngII) on cardiac function, myocardial substrate utilization, energetics, and mitochondrial function in C57Bl/6J mice and in a transgenic mouse model with cardiomyocyte specific upregulation of NOX2 (csNOX2 TG). Mice were treated with saline (sham), 50 or 400 ng/kg/min of AngII (AngII50 and AngII400) for two weeks. In vivo blood pressure and cardiac function were measured using plethysmography and echocardiography, respectively. Ex vivo cardiac function, mechanical efficiency, and myocardial substrate utilization were assessed in isolated perfused working hearts, and mitochondrial function was measured in left ventricular homogenates. AngII50 caused reduced mechanical efficiency despite having no effect on cardiac hypertrophy, function, or substrate utilization. AngII400 slightly increased systemic blood pressure and induced cardiac hypertrophy with no effect on cardiac function, efficiency, or substrate utilization. In csNOX2 TG mice, AngII400 induced cardiac hypertrophy and in vivo cardiac dysfunction. This was associated with a switch towards increased myocardial glucose oxidation and impaired mitochondrial oxygen consumption rates. Low doses of AngII may transiently impair cardiac efficiency, preceding the development of hypertrophy induced at higher doses. NOX2 overexpression exacerbates the AngII -induced pathology, with cardiac dysfunction and myocardial metabolic remodelling.


2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yina Sun ◽  
Seetha Chebolu ◽  
Denise Henry ◽  
Sandeep Lankireddy ◽  
Nissar A. Darmani

Abstract Background Methamphetamine (MA) is a non-selective monoamine releaser and thus releases serotonin (5-HT), norepinephrine (NE) and dopamine (DA) from corresponding nerve terminals into synapses. DOI ((±)-2, 5-dimethoxy-4-iodoamphetamine) is a direct-acting serotonergic 5-HT2A/C receptor agonist and induces the head-twitch response (HTR) via stimulation of 5-HT2A receptor in mice. While more selective serotonin releasers such as d-fenfluramine evoke the HTR, monoamine reuptake blockers (e.g., cocaine) suppress the DOI-evoked HTR via indirect stimulation of serotonergic 5-HT1A- and adrenergic ɑ2-receptors. Since the induction of HTR by DOI is age-dependent, we investigated whether: (1) during development MA can evoke the HTR by itself, and (2) acute pretreatment with either the selective 5-HT2A receptor antagonist EMD 281014 or low-doses of MA can: (i) modulate the DOI-induced HTR in mice across postnatal days 20, 30 and 60, and (ii) alter the DOI-induced c-fos expression in mice prefrontal cortex (PFC). To further explore the possible modulatory effect of MA on DOI-induced HTR, we investigated whether blockade of inhibitory serotonergic 5-HT1A- or adrenergic ɑ2-receptors by corresponding selective antagonists (WAY 100635 or RS 79948, respectively), can prevent the effect of MA on DOI-induced HTR during aging. Results Although neither EMD 281014 nor MA by themselves could evoke the HTR, acute pretreatment with either EMD 281014 (0.01, 0.05 and 0.1 mg/kg, i.p.) or MA (1, 2.5, 5 mg/kg, i.p.), dose-dependently suppressed the DOI-induced HTR across ages. While WAY 100635 significantly reversed the inhibitory effect of MA in 20- and 30-day old mice, RS 79948 failed to significantly counter MA’s inhibitory effect. Moreover, DOI significantly increased c-fos expressions in several PFC regions. EMD 281014 prevented the DOI-induced increases in c-fos expression. Despite the inhibitory effect of MA on DOI-induced HTR, MA alone or in combination with DOI, significantly increased c-fos expression in several regions of the PFC. Conclusion The suppressive effect of MA on the DOI-evoked HTR appears to be mainly due to functional interactions between the HTR-inducing 5-HT2A receptor and the inhibitory 5-HT1A receptor. The MA-induced increase in c-fos expression in different PFC regions may be due to MA-evoked increases in synaptic concentrations of 5-HT, NE and/or DA.


Cureus ◽  
2021 ◽  
Author(s):  
Aquila Lesko ◽  
Naciye Kalafat ◽  
Maleeha Afreen

Author(s):  
Ihnat Havrylov ◽  
Vadim Tsyvunin ◽  
Sergiy Shtrygol’ ◽  
Diana Shtrygol’

"Non-antiepileptic" drugs have a strong potential as adjuvants in multidrug-resistant epilepsy treatment. In previous study the influence of low doses of digoxin, which do not affect the myocardium, on the anticonvulsant potential of classical commonly used anti-epileptic drugs under conditions of seizures, induced by pentylenetetrazole and maximal electroshock, has been investigated. The aim of the study was to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant potential of carbamazepine and lamotrigine in experimental seizures with different neurochemical mechanisms. Material and methods: A total of 192 random-bred male albino mice weighting 22–25 g were used. Carbamazepine and lamotrigine were administered intragastrically in conditionally effective (ED50) and sub-effective (½ ED50) doses: carbamazepine at doses of 100 and 50 mg/kg; lamotrigine at doses of 25 and 12.5 mg/kg. Digoxin was administered subcutaneously at a sub-cardiotonic dose of 0.8 mg/kg as an adjuvant to carbamazepine and lamotrigine in ½ ED50. Picrotoxin (2.5 mg/kg subcutaneously); thiosemicarbazide (25 mg/kg intraperitoneally); strychnine (1.2 mg/kg subcutaneously); camphor (1000 mg/kg intraperitoneally) were used as convulsant agents. Results: It was found that digoxin not only has its own permanent anticonvulsant effect on different models of paroxysms with different neurochemical mechanisms of development, but also significantly enhances the anticonvulsant potential of carbamazepine (to a lesser extent – lamotrigine) regardless of the pathogenesis of experimental paroxysms. Conclusion: Based on the results, it can be concluded that digoxin has a high potential as an adjuvant medicine in complex epilepsy treatment because it enhances the efficiency of low-dose traditional anticonvulsants carbamazepine and lamotrigine


Author(s):  
Elzbieta Malarczyk

The allosteric protein of horseradish peroxidase (HRP) shows two main types of activity, peroxidase and oxidase, depending on the kind of low molecular effectors. The effects of very low doses of phenol, prepared by successive dilutions in water or in 75% ethanol, on initial HRP activity in oxidation of o-dianisidine or luminol were tested in a systematic manner by colorimetric and luminometric methods. Results showed that phenol dilutions, including those below Avogadro’s number, could activate or inhibit HRP in peroxidase and oxidase type reactions with a sinusoidal pattern. Km values for the studied substrates changed parallel to HRP peroxidase/oxidase activity and the maximum activity in the peroxidase reaction corresponded to the minimum activity in the oxidase reaction and vice versa. The effect also depended on the type of dilutor. The observations of the peroxidase/oxidase oscillations in the sinusoidal pattern of HRP activity, dependent on the rate of phenol dissolution and the time of preincubation, point out to the conclusion that HRP might be a good model for high dilutions research. The experiments provide strong evidence that horseradish peroxidase (HRP) is a very sensitive detector of subtle changes in the concentration of phenol used as a cofactor in the peroxidase/oxidase reaction. Keywords: HR-peroxidase, peroxidase-oxidase, phenol, hormesis, homeopathy, high dilutions.   Mudanças cinéticas na atividade da HR-peroxidade induzidas por doses muito baixas de fenol Resumo A proteína alostérica da peroxidase do rabano (HRP) mostra dois tipos principais de atividade, peroxidase e oxidase, de acordo com o tipo de efetores de baixa molecularidade. Os efeitos de doses muito baixas de fenol, preparadas através de diluições sucessivas em água ou etanol 75% na atividade inicial da HRP sobre a oxidação da o-dianisidina ou luminol for testados de modo sistemático através de métodos colorimétricos e luminométricos. Os resultados mostram que as diluições de fenol, incluindo aquelas por baixo do número de Avogadro, foram capazes de ativar ou inibir a HRP em reações de tipo peroxidade e oxidase com um padrão sinusoidal. os valores Km dos substratos estudados variaram paralelamente à atividade peroxidase/oxidase da HRP; a atividade máxima da reação peroxidase correspondeu à atividade mínima na reação oxidase e vice-versa. O efeito também se mostrou dependente do tipo do solvente. A observação das oscilações sinusoidais na atividade da HRP, dependentes da taxa de dissolução do fenol e do tempo de pré-incubação, permitem concluir que a HRP pode ser um bom modelo na pesquisa das altas diluições. Os experimentos oferecem fortes evidéncias a favor da HRP como detector muito sensível de mudanças mínimas na concentração do fenol, utilizado como cofator na reação peroxidase/oxigenase. Palavras-chave: HR-peroxidase, peroxidase-oxidase, fenol, hormese, homeopatia, altas diluições.   Cambios cinéticos en la actividad de la HR-peroxidasa inducidos por dosis muy bajas de fenol Resumen La proteína alostérica de la peroxidasa del rábano (HRP) muestra dos tipos principales de actividad, peroxidasa y oxidasa, dependiendo del tipo de efectores de baja molecularidade. Los efectos de doses muy bajas de fenol, preparadas mediante diluciones sucesivas en agua o etanol al 75% sobre la actividad inicial de la HRP sobre la oxidación de o-dianisidina o luminol fueron testados de modo sistemático mediante métodos colorimétricos y luminométricos. Los resultados muestran que las diluciones de fenol, incluyendo aquellas abajo del número de Avogadro, pudieron activar o inhibir la HRP en reacciones de tipo peroxidasa y oxidasa con un patrón sinusoidal. Los valores Km de los sustratos estudiados variaron paralelamente a la actividad peroxidasa/oxidasa de la HRP; la actividad máxima de la reacción peroxidasa correspondió a la actividad mínima en la reacción oxidasa y viceversa. El efecto también se mostró dependiente del tipo de solvente. La observación de las oscilaciones sinusoidales en la actividad de la HRP, dependientes de la tasa de disolución del fenol y del tiempo de preincubación, llevan a concluir que la HRP puede ser un buen modelo para la investigación de las altas diluciones. Los experimentos ofrecen fuertes evidencias a favor de la HRP como detector muy sensible de cambios mínimos en la concentración de fenol, utilizado como cofactor en la reacción peroxidasa/oxigenasa. Palabras-clave: HR-peroxidasa, oxidasa-peroxidasa, fenol, hormesis, homeopatía, altas diluciones.   Correspondence author: Elzbieta Malarczyk, [email protected] How to cite this article: Malarczyk E. Kinetic changes in the activity of HR-peroxidase induced by very low doses of phenol. Int J High Dilution Res [online]. 2008 [cited YYYY Mmm DD]; 7(23): 48-55. Available from: http://journal.giri-society.org/index.php/ijhdr/article/view/37/349.  


2021 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
Karyne Rangel ◽  
Fellipe O. Cabral ◽  
Guilherme C. Lechuga ◽  
João P. R. S. Carvalho ◽  
Maria H. S. Villas-Bôas ◽  
...  

(1) Background: Disinfection of medical devices designed for clinical use associated or not with the growing area of tissue engineering is an urgent need. However, traditional disinfection methods are not always suitable for some biomaterials, especially those sensitive to chemical, thermal, or radiation. Therefore, the objective of this study was to evaluate the minimal concentration of ozone gas (O3) necessary to control and kill a set of sensitive or multi-resistant Gram-positive and Gram-negative bacteria. The cell viability, membrane permeability, and the levels of reactive intracellular oxygen (ROS) species were also investigated; (2) Material and Methods: Four standard strains and a clinical MDR strain were exposed to low doses of ozone at different concentrations and times. Bacterial inactivation (cultivability, membrane damage) was investigated using colony counts, resazurin as a metabolic indicator, and propidium iodide (PI). A fluorescent probe (H2DCFDA) was used for the ROS analyses; (3) Results: No reduction in the count colony was detected after O3 exposure compared to the control group. However, the cell viability of E. coli (30%), P. aeruginosa (25%), and A. baumannii (15%) was reduced considerably. The bacterial membrane of all strains was not affected by O3 but presented a significant increase of ROS in E. coli (90 ± 14%), P. aeruginosa (62.5 ± 19%), and A. baumanni (52.6 ± 5%); (4) Conclusion: Low doses of ozone were able to interfere in the cell viability of most strains studied, and although it does not cause damage to the bacterial membrane, increased levels of reactive ROS are responsible for causing a detrimental effect in the lipids, proteins, and DNA metabolism.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Suna Aydin ◽  
Kader Ugur ◽  
Hanifi Yalcin ◽  
İbrahim Sahin ◽  
Ramazan Fazil Akkoc ◽  
...  

Abstract COVID-19 is the most devastating pandemic situation we have experienced in our age, affecting all systems. Although it affects all systems, it shows its most important effect through thrombophilia. Therefore, the possible cause of sudden death due to COVID-19 may be embolism caused by thrombophilia. D-dimer amounts increase due to COVID-19. The thrombosis is associated with sudden death in COVID-19 disease in populations. Since individuals with thrombophilia will be more prone to death due to COVID-19, it may be appropriate to administer low doses of Clexane (Enoxaparin sodium) or low-weight heparin for prophylactic purposes in order to consider these individuals at high risk and to prevent deaths. Moreover, in order not to risk the lives of healthcare professionals with thrombophilia, it would be appropriate to keep them away from individuals with COVID-19 disease and to employ them in different healthcare services according to their fields of expertise. It should also not be forgotten that different symptoms related to COVID-19 appear day by day, these different symptoms probably show that the virus has undergone mutations in order to survive, but no matter what, its effect on thrombophilia has not been eliminated yet. This compilation aims to present the reasons and causes of death due to COVID-19, possible treatment options, and thrombophilia panel tests and new parameters that may have a place in the meticulous interpretation of these tests and possible etiopathology in the light of current information. Therefore, presenting this information in a rational manner and keeping the parameters of the thrombophilia panel under strict control predict that the deaths due to the virus will be partially reduced.


2021 ◽  
Vol 11 (1) ◽  
pp. 59
Author(s):  
Mitchell A. Head ◽  
Laura K. McColl ◽  
Anica Klockars ◽  
Allen S. Levine ◽  
Pawel K. Olszewski

A recent case report has shown that an adjunctive oxytocin + naltrexone (OT + NTX) treatment promoted more robust hypophagia and body weight reduction than OT alone in an adolescent male with hypothalamic obesity after craniopharyngioma resection. Thus far, there has been no basic research in adolescent laboratory animals that would examine whether the benefit of OT + NTX on appetite extends onto adolescent individuals without surgically induced overeating. Thus, here we examined whether low doses of combined OT + NTX acutely affect post-deprivation intake of energy-dense, standard chow; intake of energy-dense and palatable high-fat high-sugar (HFHS) diet; or calorie-dilute, palaTable 10% sucrose solution without deprivation in adolescent male rats. We assessed whether OT + NTX decreases water intake after water deprivation or produces a conditioned taste aversion (CTA). Finally, by using c-Fos immunoreactivity, we determined changes in activity of feeding-related brain areas after OT + NTX. We found that individual subthreshold doses of OT and NTX decreased feeding induced by energy and by palatability. Significant c-Fos changes were noted in the arcuate and dorsomedial hypothalamic nuclei. The hypophagic doses of OT + NTX did not suppress water intake in thirsty rats and did not cause a CTA, which suggests that feeding reduction is not a secondary effect of gastrointestinal discomfort or changes in thirst processing. We conclude that OT + NTX is an effective drug combination to reduce appetite in adolescent male rats.


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