scholarly journals Can Lipoic Acid Attenuate Cardiovascular Disturbances Induced by Ethanol and Disulfiram Administration Separately or Jointly in Rats?

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Anna Bilska-Wilkosz ◽  
Magdalena Kotańska ◽  
Magdalena Górny ◽  
Barbara Filipek ◽  
Małgorzata Iciek

The exogenous lipoic acid (LA) is successfully used as a drug in the treatment of many diseases. It is assumed that after administration, LA is transported to the intracellular compartments and reduced to dihydrolipoic acid (DHLA) which is catalyzed by NAD(P)H-dependent enzymes. The purpose of this study was to investigate whether LA can attenuate cardiovascular disturbances induced by ethanol (EtOH) and disulfiram (DSF) administration separately or jointly in rats. For this purpose, we measured systolic and diastolic blood pressure, recorded electrocardiogram (ECG), and estimated mortality of rats. We also studied the activity of aldehyde dehydrogenase (ALDH) in the rat liver. It was shown for the first time that LA partially attenuated the cardiac arrhythmia (extrasystoles and atrioventricular blocks) induced by EtOH and reduced the EtOH-induced mortality of animals, which suggests that LA may have a potential for use in cardiac disturbance in conditions of acute EtOH intoxication. The administration of EtOH, LA, and DSF separately or jointly affected the ALDH activity in the rat liver since a significant decrease in the activity of the enzyme was observed in all treatment groups. The results indicating that LA is an inhibitor of ALDH activity are very surprising.

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Cameron Radford ◽  
John Weldon McNutt ◽  
Tracey Rogers ◽  
Ben Maslen ◽  
Neil Jordan

AbstractEyespots evolved independently in many taxa as anti-predator signals. There remains debate regarding whether eyespots function as diversion targets, predator mimics, conspicuous startling signals, deceptive detection, or a combination. Although eye patterns and gaze modify human behaviour, anti-predator eyespots do not occur naturally in contemporary mammals. Here we show that eyespots painted on cattle rumps were associated with reduced attacks by ambush carnivores (lions and leopards). Cattle painted with eyespots were significantly more likely to survive than were cross-marked and unmarked cattle, despite all treatment groups being similarly exposed to predation risk. While higher survival of eyespot-painted cattle supports the detection hypothesis, increased survival of cross-marked cattle suggests an effect of novel and conspicuous marks more generally. To our knowledge, this is the first time eyespots have been shown to deter large mammalian predators. Applying artificial marks to high-value livestock may therefore represent a cost-effective tool to reduce livestock predation.


2012 ◽  
Vol 3 (5) ◽  
pp. 342-349 ◽  
Author(s):  
S. Y. Bai ◽  
D. I. Briggs ◽  
M. H. Vickers

An adverse prenatal environment may induce long-term metabolic consequences, in particular hypertension and cardiovascular disease. A maternal low-protein (LP) diet is well known to result in increased blood pressure (BP) in offspring. Choline has been shown to have direct BP-reducing effects in humans and animals. It has been suggested that endogenous choline synthesis via phosphatidylcholine is constrained during maternal LP exposure. The present study investigates the effect of choline supplementation to mothers fed a LP diet during pregnancy on systolic BP (SBP) in offspring as measured by tail-cuff plethysmography. Wistar rats were assigned to one of three diets to be fed ad libitum throughout pregnancy: (1) control diet (CONT, 20% protein); (2) an LP diet (9% protein); and (3) LP supplemented with choline (LP + C). Dams were fed the CONT diet throughout lactation and offspring were fed the CONT diet from weaning for the remainder of the trial. At postnatal day 150, SBP and retroperitoneal fat mass was significantly increased in LP offspring compared with CONT animals and was normalized in LP + C offspring. Effects of LP + C reduction in SBP were similar in both males and females. Plasma choline and phosphatidylcholine concentrations were not different across treatment groups, but maternal choline supplementation resulted in a significant reduction in homocysteine concentrations in LP + C offspring compared with LP and CONT animals. The present trial shows for the first time that maternal supplementation with dietary choline during periods of LP exposure can normalize increased SBP and fat mass observed in offspring in later life.


Author(s):  
Anna Bilska-Wilkosz ◽  
Magdalena Kotańska ◽  
Magdalena Górny ◽  
Barbara Filipek ◽  
Małgorzata Iciek

The aim of the study presented here was an attempt to answer the question posed in the title: Is the mechanism of nitroglycerin tolerance associated with aldehyde dehydrogenase (ALDH) activity? Here, we investigated the effect of administration (separately or jointly) of lipoic acid (LA), nitroglycerin (GTN), and disulfiram (DSF; an irreversible in vivo inhibitor of all ALDH isozymes (including ALDH2)), on the development of tolerance to GTN. We also assessed the total activity of ALDH in the rat liver homogenates. Our data revealed that not only DSF and GTN inhibited the total ALDH activity in the rat liver, but LA also proved to be an inhibitor of this enzyme. At the same time, the obtained results demonstrated that the GTN tolerance did not develop in GTN, DSF and LA jointly treated rats, but did develop in GTN and DSF jointly treated rats. This means that the ability of LA to prevent GTN tolerance is not associated with the total ALDH activity in the rat liver. In this context, the fact that animals jointly receiving GTN and DSF developed tolerance to GTN, and in animals that in addition to GTN and DSF also received LA such tolerance did not develop, is – in our opinion – a sufficient premise to conclude that the nitrate tolerance certainly is not caused by a decrease in the activity of any of the ALDH isoenzymes present in the rat liver, including ALDH2. However, many questions still await an answer, including the basic one: What is the mechanism of tolerance to nitroglycerin?


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Amanda E Garza ◽  
Luminita Pojoga ◽  
Rene Baudrand ◽  
Burhanuddin Moize ◽  
Tham Yao ◽  
...  

Background: We recently demonstrated that mice lacking one copy of the striatin gene (Strn+/-) have salt sensitivity of blood pressure (BP) as compared with WT mice. To determine whether Strn+/- mice have increased sensitivity to aldosterone (ALDO), we assessed the effect on blood pressure of an ALDO infusion in WT and Strn+/- mice fed a liberal sodium diet. Methods: In this study we used 12 week old WT and Strn+/- littermate male mice. For each genotype, mice were placed on HS diet and randomized to either: 1) placebo 2) ALDO (200 μg/Kg/day) or 3) ALDO plus 100 mg/kg/day eplerenone. BP was measured by tail cuff plethysmography at baseline and after treatment. After 21 days of treatment, animals were placed in metabolic cages for 24 hours. Finally, animals were sacrificed and organs excised. Primary endpoints were BP, renal immunohistochemistry, protein analysis by western blot and mRNA expression by RT-PCR. Results: BP increased significantly in Strn+/- mice treated with ALDO (ΔBP: 12 ± 4 mmHg, p=0.03) but not placebo (ΔBP 6± 6 mmHg); the BP effect of ALDO was blunted by eplerenone (Δ 6 ± 3 mmHg). In contrast, none of the treatments had a significant effect on BP in WT mice. Kidney weight was significantly increased after 3 weeks of ALDO treatment in both WT and Strn+/- mice and this increase in kidney weight was prevented by treatment with eplerenone, with no difference between genotypes. WT mice had an increase in glomerular volume (GV) in HS/ALDO treated that was blunted by eplerenone. Interestingly, Strn+/- mice had increased GV across all 3 treatment groups compared with WT mice. pAkt/Akt ratios were reduced in Strn+/- mice versus WT mice across all treatments. Classic genomic MR targets (ENaC and SGK1) and non-genomic targets (pAkt/Akt) were significantly modulated in kidney tissue of Strn+/- mice compared to WT mice with chronic ALDO. Conclusion: Strn+/- mice have an increased sensitivity to infused ALDO (increased BP response and increased rise in renal ENaC and SGK1 protein) as compared to WT mice. Since loss of striatin directly reduces nongenomic not genomic action of ALDO, this study demonstrates for the first time that modifying the nongenomic pathway may under chronic, in vivo conditions led to increased sensitivity to the genomic actions of ALDO.


2020 ◽  
Vol 16 ◽  
Author(s):  
Seiji Umemoto ◽  
Toshio Ogihara ◽  
Masunori Matsuzaki ◽  
Hiromi Rakugi ◽  
Kazuyuki Shimada ◽  
...  

Background: In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events) three benidipine (a calcium channel blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40–85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional angiotensin receptor blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group. Objective and Methods: We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients. Results: A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events p=0.92 renal events p=0.16 log-rank test. Conclusions: Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there is no enough these events to compare the difference in the three treatment groups.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Elisa Mejía-Mejía ◽  
James M. May ◽  
Mohamed Elgendi ◽  
Panayiotis A. Kyriacou

AbstractHeart rate variability (HRV) utilizes the electrocardiogram (ECG) and has been widely studied as a non-invasive indicator of cardiac autonomic activity. Pulse rate variability (PRV) utilizes photoplethysmography (PPG) and recently has been used as a surrogate for HRV. Several studies have found that PRV is not entirely valid as an estimation of HRV and that several physiological factors, including the pulse transit time (PTT) and blood pressure (BP) changes, may affect PRV differently than HRV. This study aimed to assess the relationship between PRV and HRV under different BP states: hypotension, normotension, and hypertension. Using the MIMIC III database, 5 min segments of PPG and ECG signals were used to extract PRV and HRV, respectively. Several time-domain, frequency-domain, and nonlinear indices were obtained from these signals. Bland–Altman analysis, correlation analysis, and Friedman rank sum tests were used to compare HRV and PRV in each state, and PRV and HRV indices were compared among BP states using Kruskal–Wallis tests. The findings indicated that there were differences between PRV and HRV, especially in short-term and nonlinear indices, and although PRV and HRV were altered in a similar manner when there was a change in BP, PRV seemed to be more sensitive to these changes.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3861
Author(s):  
Guo-Ming Dong ◽  
Hang Yu ◽  
Li-Bin Pan ◽  
Shu-Rong Ma ◽  
Hui Xu ◽  
...  

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.


Electronics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 679
Author(s):  
Jongpal Kim

An instrumentation amplifier (IA) capable of sensing both voltage and current at the same time has been introduced and applied to electrocardiogram (ECG) and photoplethysmogram (PPG) measurements for cardiovascular health monitoring applications. The proposed IA can switch between the voltage and current sensing configurations in a time–division manner faster than the ECG and PPG bandwidths. The application-specific integrated circuit (ASIC) of the proposed circuit design was implemented using 180 nm CMOS fabrication technology. Input-referred voltage noise and current noise were measured as 3.9 µVrms and 172 pArms, respectively, and power consumption was measured as 34.9 µA. In the current sensing configuration, a current noise reduction technique is applied, which was confirmed to be a 25 times improvement over the previous version. Using a single IA, ECG and PPG can be monitored in the form of separated ECG and PPG signals. In addition, for the first time, a merged ECG/PPG signal is acquired, which has features of both ECG and PPG peaks.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 273
Author(s):  
Marc Schargus ◽  
Catharina Busch ◽  
Matus Rehak ◽  
Jie Meng ◽  
Manuela Schmidt ◽  
...  

The aim of this study was to compare the efficacy of trabeculectomy (TE), single XEN microstent implantation (solo XEN) or combined XEN implantation and cataract surgery (combined XEN) in primary open-angle glaucoma cases, naïve to prior surgical treatment, using a monocentric retrospective comparative cohort study. Intraocular pressure (IOP) and the number of IOP-lowering drugs (Meds) were monitored during the first 24 months after surgery. Further disease progression was monitored using peripapillary retinal nerve fiber layer (RNFL) thickness examinations using spectral domain optical coherence tomography (OCT) as well as visual acuity (VA) and visual field (VF) tests. In the TE group (52 eyes), the mean IOP decreased from 24.9 ± 5.9 to 13.9 ± 4.2 mmHg (p < 0.001) and Meds decreased from 3.2 ± 1.2 to 0.5 ± 1.1 (p < 0.001). In the solo XEN (38 eyes) and the combined XEN groups, the mean IOP decreased from 24.1 ± 4.7 to 15.7 ± 3.0 mmHg (p < 0.001) and 25.4 ± 5.6 to 14.7 ± 3.2 mmHg (p < 0.001), while Meds decreased from 3.3 ± 0.8 to 0.8 ± 1.2 (p < 0.001) and 2.7 ± 1.2 to 0.4 ± 1.0 (p < 0.001), respectively. The VF and VA indices showed no sign of further deterioration, the RNFL thickness further decreased in all treatment groups after surgery. TE and XEN led to comparable reductions in IOP and Meds. Although the VA and VF indices remained unaltered, the RNFL thickness continuously decreased in all treatment groups during the 24-month follow-up.


Author(s):  
Giacomo Pucci ◽  
Edoardo Santoni ◽  
Valeria Bisogni ◽  
Camilla Calandri ◽  
Alberto Cerasari ◽  
...  

AbstractAtrial fibrillation (AF), the commonest sustained cardiac arrhythmia affecting the adult population, is often casually discovered among hospitalized people. AF onset is indeed triggered by several clinical conditions such as acute inflammatory states, infections, and electrolyte disturbance, frequently occurring during the hospitalization. We aimed to evaluate whether systematic AF screening, performed through an automated oscillometric blood pressure (BP) device (Microlife WatchBP Office AFIB, Microlife AG, Switzerland), is effective for detecting AF episodes in subjects admitted to an Internal Medicine ward. 163 patients consecutively hospitalized at the Unit of Internal Medicine of the “Santa Maria” Terni University Hospital between November 2019 and January 2020 (mean age ± standard deviation: 77 ± 14 years, men proportion: 40%) were examined. Simultaneously with BP measurement and AF screening, a standard 12-lead electrocardiogram (ECG) was performed in all subjects. AF was diagnosed by ECG in 29 patients (18%). AF screening showed overall 86% sensitivity and 96% specificity. False negatives (n = 4) had RR-interval coefficient of variation lower than true positives (n = 25, p < 0.01), suggesting a regular ventricular rhythm during AF. The repeated evaluation substantially confirmed the same level of agreement. AF screening was positive in all patients with new-onset AF (n = 6, 100%). Systematic AF screening in patients admitted to Internal Medicine wards, performed using the Microlife WatchBP Office AFIB, is feasible and effective. The opportunity to implement such technology in daily routine clinical practice to prevent undiagnosed AF episodes in hospitalized patients should be the subject of further research.


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