N-Palmitoylethanolamine-oxazoline (PEA-OXA): A new therapeutic strategy to reduce neuroinflammation, oxidative stress associated to vascular dementia in an experimental model of repeated bilateral common carotid arteries occlusion

2019 ◽  
Vol 125 ◽  
pp. 77-91 ◽  
Author(s):  
Daniela Impellizzeri ◽  
Rosalba Siracusa ◽  
Marika Cordaro ◽  
Rosalia Crupi ◽  
Alessio Filippo Peritore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Dementia ◽  
Experimental Model ◽  
Therapeutic Strategy ◽  
Carotid Arteries ◽  
Common Carotid Arteries

scholarly journals Serum Oxidative Stress Markers are not Associated with Renal and Common Carotid Arteries Arteriosclerotic Vascular Changes in Patients with Gout

2019 ◽  
Vol 46 (3) ◽  
pp. 37-43
Author(s):  
R. Gancheva ◽  
A. Kundurdjiev ◽  
G. Nikolova ◽  
M. Ivanova ◽  
T. Kundurdjiev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carotid Arteries ◽  
Ex Vivo ◽  
Gouty Arthritis ◽  
Resistive Index ◽  
Serum Levels ◽  
Renal Resistive Index ◽  
Serum Concentrations ◽  
Vascular Changes ◽  
Common Carotid Arteries

Abstract Objective: To establish the association between serum levels of reactive oxygen species (ROS) products, nitric oxide (NO) radicals and ascorbate radicals with renal resistive index (RRI), common carotid artery resistive index (CCARI) and intima-media thickness (IMT) in gout patients, and to find out whether the connection is more pronounced when tophi are present. Methods: A cross-sectional study including 71 consecutive gout patients, divided into two groups according to the presence of subcutaneous tophi. Serum concentrations of ROS products, NO radicals and ascorbate radicals were determined by ex vivo electron paramagnetic resonance (EPR) study. RRI was measured in both kidneys at the level of interlobar arteries with 3.5 MHz transducer. By applying ultrasound of the common carotid arteries, conducted with 10 MHz linear transducer CCARI and IMT were measured. Results: Gouty arthritis without tophi and gouty tophi subjects were age-matched. Serum uric acid and distribution of conventional cardiovascular risk factors was equal in the groups. However, in tophi patients CRP and the number of individuals who had suffered a cardiovascular event were higher. In the two stages of the disease serum levels of ROS products, NO radicals, ascorbate radicals, as well as RRI and CCARI were comparable but intima-media was thicker in gouty tophi. Serum concentrations of ROS products, NO radicals and ascorbate radicals did not correlate with RRI, CCARI and IMT. Among untreated and treated with Allopurinol or Febuxostat patients the means of ROS products, NO radicals, ascorbate radicals, RRI, CCARI and IMT were similar. Conclusions: In the earlier and advanced stage of the disease we found no difference in oxidative stress level but the degree of inflammation was higher in tophi subjects. No connection was established between serum ROS products, NO radicals and ascorbate radicals with renal and carotid arteries arteriosclerotic vascular changes. We suggest that in gout individuals intrinsic inflammation has a leading role in the process of atherogenesis.

scholarly journals Synergism of the pharmacological effect of glycine and thiotriazoline

Pathologia ◽  
2021 ◽  
Vol 18 (1) ◽  
pp. 26-32
Author(s):  
I. F. Bielenichev ◽  
A. A. Yehorov
Keyword(s):  
Oxidative Stress ◽  
Energy Metabolism ◽  
Cerebrovascular Accident ◽  
Carotid Arteries ◽  
Mitochondrial Fraction ◽  
Intragastric Administration ◽  
Experimental Animals ◽  
Acute Cerebrovascular Accident ◽  
Mitochondrial Pore ◽  
Common Carotid Arteries

Aim. To establish the effect of the glycine and thiotriazoline (4:1) combination on the parameters of the energy production of the mitochondria of the rat brain under the conditions of simulating an acute cerebrovascular accident. Materials and methods. The experimental part was performed on 90 male Wistar rats weighing 180–200 g. To model acute cerebrovascular accident (ACVA) by ischemic type, a classical model was used, where common carotid arteries had been ligated bilaterally. All animals were divided into 5 experimental groups: the first – intact (sham-operated rats, which during anesthesia had their common carotid arteries separated without ligation); the second – rats with ACVA (control); the third – rats with ACVA, which underwent intragastric administration of glycine at a dose of 200 mg/kg in the form of a tablet mass every day for 4 days; the fourth – rats with stroke, which every day for 4 days underwent intragastric administration of a combination of glycine and thiotriazoline (4:1) in the form of a tablet mass; the fifth – rats with ACVA, which underwent every day intragastric administration of piracetam in the form of a tablet mass at a dose of 500 mg/kg. The sampling of biological material (brain) for research was carried out on the fourth day of the experiment according to the standard method. The mitochondrial fraction was isolated by differential centrifugation in a refrigerated centrifuge. The manifestations of mitochondrial dysfunction, have been spectrophotometrically studied according to the degree of opening of the mitochondrial pore (MP) and mitochondrial transmembrane potential (Ψ). The assessment of the intensity of oxidative stress was determined by the markers of protein oxidative modification – aldehydephenylhydrazone (APH) and ketonedinitrophenylhydrazone (KPH) – spectrophotometrically. The state of energy metabolism was determined by the level of the most significant intermediates – ATP, lactate, succinate and malate. Results. In the group of animals with ACVA modeling, we noted a decrease in the level of ATP in mitochondria by 1.55 times, an increase in lactate content by 1.1 times, a decrease in SDH activity by 3.8 times and a decrease in succinate concentration by 1.1 times relative to the corresponding data of intact groups. Administration of a combination of glycine and thiotriazoline to experimental animals on the fourth day of ACVA modeling led to a 1.9-fold decrease in the opening of the mitochondrial pore and an increase in the charge of the inner mitochondrial membrane by 1.2 times, an increase in ATP in the mitochondrial fraction by 1.1 times, an increase in SDH activity by 3 times, and the activity of NAD-MDH – by 3.7 times, against the background of a decrease in the level of APH by 76.6 % and KPH by 80.7 %, relative to the group of animals with modeling of stroke by ischemic type. Conclusions. Modeling of ACVA leads to the initiation of oxidative stress and the development of an imbalance of energy metabolism intermediates in the brain mitochondria of experimental animals. Administration of a combination of glycine and thiotriazoline leads to a decrease in oxidative damage to mitochondria, increases the production of ATP due to the activation of compensatory mitochondrial-cytosolic shunts, mainly in malate-aspartate and succinate oxidase. In terms of the degree of influence on the indicators of energy metabolism, the combination of glycine and thiotriazoline reliably exceeds the similar actions of glycine and the reference drug - piracetam.

scholarly journals N‐Palmitoylethanolamine‐oxazoline (PEA‐OXA): a new therapeutic strategy to reduce neuroinflammation and oxidative stress associated to vascular dementia

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Salvatore Cuzzocrea ◽  
Daniela Impellizzeri ◽  
Rosalba Siracusa ◽  
Marika Cordaro ◽  
Rosalia Crupi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Dementia ◽  
Therapeutic Strategy ◽  
And Oxidative Stress

scholarly journals Effect of low-dose Levamlodipine Besylate in the treatment of vascular dementia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kai-Xin Yao ◽  
Hang Lyu ◽  
Mei-Hua Liao ◽  
Lin Yang ◽  
Yin-Ping Gao ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Dementia ◽  
Carotid Arteries ◽  
Low Dose ◽  
Therapeutic Potential ◽  
Vehicle Group ◽  
Mice Model ◽  
Complex Disorder ◽  
Common Carotid Arteries ◽  
The Brain

AbstractVascular dementia (VaD) is a complex disorder caused by reduced blood flow in the brain. However, there is no effective pharmacological treatment option available until now. Here, we reported that low-dose levamlodipine besylate could reverse the cognitive impairment in VaD mice model of right unilateral common carotid arteries occlusion (rUCCAO). Oral administration of levamlodipine besylate (0.1 mg/kg) could reduce the latency to find the hidden platform in the MWM test as compared to the vehicle group. Furthermore, vehicle-treated mice revealed reduced phospho-CaMKII (Thr286) levels in the hippocampus, which can be partially restored by levamlodipine besylate (0.1 mg/kg and 0.5 mg/kg) treatment. No significant outcome on microglia and astrocytes were observed following levamlodipine besylate treatment. This data reveal novel findings of the therapeutic potential of low-dose levamlodipine besylate that could considerably enhance the cognitive function in VaD mice.

scholarly journals Bilateral Carotid Artery Occlusion and Cochlear Oxidative Stress and Hearing Loss in Rats

2020 ◽  
Vol 11 (6) ◽  
pp. 821-830
Author(s):  
Hamed Fanaei ◽  
◽  
Akram Pourbakht ◽  
Sadegh Jafarzadeh ◽  
◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carotid Artery ◽  
Biochemical Analysis ◽  
Carotid Arteries ◽  
Auditory Brainstem ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Bilateral Carotid ◽  
Common Carotid Arteries ◽  
Bilateral Carotid Artery

Introduction: This study aimed to evaluate the effects of bilateral carotid artery occlusion on cochlear oxidative stress and hearing status in rats. Methods: The rats were divided into two sets. The first set was used for electrophysiological recording (click and 4 kHz tone burst auditory brainstem responses and electrocochleography) on the day before surgery and then on the first, fourth, and seventh days after surgery. Animals of the second set were used for biochemical analysis. The cochlea of animals in the second set was collected on the first, fourth, and seventh days after carotids occlusion for biochemical analysis. For the control groups, no carotids occlusion was done. For ischemia induction, both common carotid arteries were occluded for 20 minutes. Results: Electrophysiological analysis showed that burst auditory brainstem thresholds significantly elevated after common carotid arteries occlusion on the first, fourth, and seventh days after surgery with abnormal electrocochleography results at 75%, 70%, and 85% on the first, fourth, and seventh days after surgery, respectively. The electrophysiological finding confirmed by biochemical results that showed malondialdehyde and nitric oxide levels increased and superoxide dismutase and catalase activities decreased after occlusion in cochlea tissue. Conclusion: This study showed that bilateral common carotid artery occlusion increases cochlear oxidative stress and induces hearing loss in rats.

Effect of carvedilol on the redox-status of plasma low-molecular-weight aminothyols in rats with acute cerebral ischemia

2018 ◽  
pp. 12-18
Author(s):  
К.А. Никифорова ◽  
В.В. Александрин ◽  
П.О. Булгакова ◽  
А.В. Иванов ◽  
Э.Д. Вирюс ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cerebral Ischemia ◽  
Carotid Arteries ◽  
Redox Status ◽  
Global Cerebral Ischemia ◽  
Low Molecular Weight ◽  
Adrenergic Antagonist ◽  
Acute Cerebral Ischemia ◽  
Common Carotid Arteries ◽  
Reduced Forms

Цель. Установить влияние неспецифического адреноблокатора карведилола на редокс-статус низкомолекулярных аминотиолов (цистеин, гомоцистеин, глутатион) в плазме крови при моделировании глобальной ишемии головного мозга у крыс. Методика. Нами была использована модель глобальной ишемии (пережатие общих сонных артерий с геморрагией длительностью 15 мин). Препарат вводили за 1 ч до операции. Уровни аминотиолов измеряли через 40 мин после начала реперфузии. Анализ уровня аминотиолов проводили методом жидкостной хроматографии. Результаты. Установлено, что у крыс, не подвергавшихся ишемии, карведилол в дозе 10 мг/кг вызывает рост редокс-статуса цистеина и глутатиона (в 3 и 3,5 раза соответственно по сравнению с контролем, p = 0,04 и p = 0,008) за счет увеличения их восстановленных форм. При ишемии данного эффекта не наблюдалось. Редокс-статус у крыс с ишемией на фоне карведилола (Цис = 0,85 ± 0,14%, Глн = 1,8 ± 0,7%, Гцис = 1,1 ± 0,8%) оставался таким же низким, как и у крыс с ишемией без введения карведилола (р > 0,8). Заключение. Полученный результат демонстрирует, что в условиях ишемии головного мозга карведилол не оказывает эффекта на гомеостаз аминотиолов плазмы крови, несмотря на выраженный антиоксидантный эффект в нормальных условиях. Aim. Effect of a nonspecific adrenergic antagonist carvedilol on the redox status of plasma low-molecular-weight aminothiols (cysteine, homocysteine, glutathione) was studied in rats with global cerebral ischemia (occlusion of common carotid arteries with hemorrhage). Methods. A model of global ischemia (occlusion of common carotid arteries with 15-min hemorrhage) was used. The drugs were administered one hour before the operation. Aminothiol levels were measured by HPLC with UV detection at 40 minutes after the onset of reperfusion. Results. Carvedilol 10 mg/kg increased the redox status of cysteine and glutathione in rats not exposed to ischemia (3 and 3.5 times, respectively, compared with the control, p = 0.04 and p = 0.008, respectively) but not of homocysteine, by increasing their reduced forms. However, this effect was not observed in ischemia. In rats with ischemia treated with carvedilol, the redox status (Cys = 0.85 ± 0.14%, GSH = 1.8 ± 0.7%, Hcys = 1.1 ± 0.8%) remained low similar to that in rats with ischemia not treated with carvedilol (p >0.8, 0.8, and 0.9, respectively). Conclusion. Carvedilol did not affect the homeostasis of blood plasma thiols in cerebral ischemia despite the pronounced antioxidant effect under the normal conditions.

Emerging Biomarkers and Contributing Factors of Prostate Cancer.

2020 ◽  
Vol 16 ◽  
Author(s):  
Mini Dahiya ◽  
Monu Yadav ◽  
Kalpana Nagpal ◽  
Nidhi Sharma ◽  
Kajal Joshi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Tumor Suppressor Genes ◽  
Therapeutic Strategy ◽  
Cannabinoid Receptors ◽  
Contributing Factors ◽  
Cause Of Deaths ◽  
Pharmaceutical Industries ◽  
Brca1 Brca2 ◽  
Molecular Pathophysiology

: Prostate Cancer (PC) is one the most prominent cause of deaths in males worldwide especially in western countries. The exhaustive research into prostate cancer to date has demonstrated ELAC2, RNASEL, MSR1, NBS1, CHEK2, MYC, BCL-2, c-Kit, tumor suppressor genes, BRCA1, BRCA2, PACE4, GSTP1, PTEN,CDKN1B, NKX3.1, KLF6, FOXA1, Retinoblastoma, p53, androgen receptor, kallikreins, ETS, CYP17, SRD5A2, E-cadherin, KAI1/CD82, hepsin, AMACR, PIM1, MTA-1, EZH2, EPHB2, growth factors & its receptors, cannabinoid receptors, annexins, oxidative stress and inflammation are entailed changes underlying the initiation, development, and progression of PC. Furthermore, oncology would shift from a reactive to proactive discipline so exploring these targets open new area of research. Therefore, the present review is focused on molecular pathophysiology biomarkers for the progression of PC that would encourage the researchers and pharmaceutical industries to investigate potential therapeutic strategy to overcome demerits of currently available clinically therapies.

scholarly journals Synchronous Carotid Bifurcation Endarterectomy and Retrograde Kissing Stenting of the Innominate and Left Common Carotid Artery in a Patient with a Bovine Aortic Arch

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Alessandro Robaldo ◽  
Guido Carignano ◽  
Alberto Balderi ◽  
Claudio Novali
Keyword(s):  
Carotid Artery ◽  
Aortic Arch ◽  
Common Carotid Artery ◽  
Carotid Arteries ◽  
High Risk Patient ◽  
Carotid Bifurcation ◽  
Left Common Carotid Artery ◽  
The Right ◽  
Bovine Aortic Arch ◽  
Common Carotid Arteries

Management of the symptomatic multiple stenosis of supra-aortic vessels (MSSVs) in a “bovine” aortic arch (BAA) configuration is infrequently reported. The optimal treatment choice remains debatable. A successful hybrid treatment for a proximal critical stenosis of the innominate and left common carotid artery was performed in a high-risk patient with a tandem symptomatic lesion in the right carotid bifurcation and a concentric vulnerable plaque in the bovine trunk. This case supports the feasibility, safety, and efficacy of a combined carotid bifurcation endarterectomy and retrograde kissing stenting of common carotid arteries with cerebral protection after evaluation of radiological, anatomical, and clinical parameters.

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