Guanidinoacetic acid provides superior cardioprotection to its combined use with betaine and (or) creatine in HIIT-trained rats.

This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants ( O 2 - , H2O2, NO 2 - , and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the cross-sectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario.

Melissa officinalis L. Supplementation Provides Cardioprotection in a Rat Model of Experimental Autoimmune Myocarditis.

Due to existing evidence regarding antioxidant and anti-inflammatory effects of Melissa officinalis extracts (MOEs), this study was aimed at investigating the potential of ethanolic MOE to prevent the development of myocarditis and its ability to ameliorate the severity of experimental autoimmune myocarditis (EAM) by investigating MOE effects on in vivo cardiac function, structure, morphology, and oxidative stress parameters. A total of 50 7-week-old male Dark Agouti rats were enrolled in the study and randomly allocated into the following groups: CTRL, nontreated healthy rats; EAM, nontreated rats with EAM; MOE50, MOE100, and MOE200, rats with EAM treated with either 50, 100, or 200 mg/kg of MOE for 3 weeks per os. Myocarditis was induced by immunization of the rats with porcine myocardial myosin (0.5 mg) emulsion on day 0. Cardiac function and dimensions of the left ventricle (LV) were assessed via echocardiography. Additionally, the blood pressure and heart rate were measured. On day 21, rats were sacrificed and the hearts were isolated for further histopathological analyses (H/E and Picrosirius red staining). The blood samples were collected to determine oxidative stress parameters. The EAM group characteristically showed greater LV wall thickness and lower ejection fraction (50.33 ± 7.94% vs. 84.81 ± 7.74%) and fractional shortening compared to CTRL (p < 0.05). MOE significantly improved echocardiographic parameters (EF in MOE200 81.44 ± 5.51%) and also reduced inflammatory infiltrate (by 88.46%; p < 0.001) and collagen content (by 76.39%; p < 0.001) in the heart tissues, especially in the MOE200 group compared to the EAM group. In addition, MOEs induced a significant decrease of prooxidants production (O2 -, H2O2, and TBARS) and improved antioxidant defense system via increase in GSH, SOD, and CAT compared to EAM, with medium and high dose being more effective than low dose (p < 0.05). The present study suggests that ethanolic MOEs, especially in a 200 mg/kg dose, improve cardiac function and myocardial architecture, possibly via oxidative stress mitigation, thus preventing heart remodeling, development of dilated cardiomyopathy, and subsequent heart failure connected with EAM. MOEs might be considered as a potentially helpful adjuvant therapy in patients with autoimmune myocarditis.

Black chokeberry Aronia melanocarpa extract reduces blood pressure, glycemia and lipid profile in patients with metabolic syndrome: a prospective controlled trial.

The aim of the study was to examine the effect of 4-week supplementation of Alixir 400 PROTECT® (Standardized Aronia L. Melanocarpa Extract Extract-SAE) on clinical and biochemical parameters in patients with confirmed metabolic syndrome (MetS). This study was designed as a prospective open-label clinical case-series study with 28 days of follow-up with cases selected and followed during the period from February 1, 2018 to November 2019. The study included 143 male and female patients with MetS who were subjected to SAE. SAE supplementation significantly altered SP, BP as well as HR values. After 2 weeks, CHOL levels significantly decreased in the fMetS-DM group compared to the baseline values in this group, while the LDL levels significantly decreased in the fMetS group. Triglycerides significantly decreased only after 4 weeks of SAE treatment in diabetic groups of patients (fMetS-DM and mMetS-DM) compared to the baseline, while in non-diabetic groups this marker was not significantly altered. Increased polyphenols or SAE consumption is correlated with a positive effect on body weight, total cholesterol, low and high-density lipoproteins, blood pressure and glycemia. Increasing consumption of polyphenol-rich foods could be a promising strategy to reduce cardiovascular risk.

Cisplatin and cisplatin analogues perfusion through isolated rat heart: the effects of acute application on oxidative stress biomarkers.

Drug-induced oxidative stress can occur in numerous tissues and organ systems (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy with cisplatin is associated with side effects to which oxidative stress may contribute. We have compared the influences of cisplatin (reference compound) and its' analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and chloro(2,2':6',2″-terpyridine)platinum(II)) in a model of isolated rat heart using the Langendorff technique. The production of oxidative stress biomarkers, antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs were studied. Cisplatin and the analogues were perfused at concentration of 10-6 and 10-5 M during 30 min. The results of this study showed that examined platinum complexes had different ability to induce oxidative stress of isolated perfused rat heart. Varying the carrier ligands, such as 1,2-diaminocyclohexane and 2,2':6',2″-terpyridine, related to amino ligands (cisplatin) directly influenced the strength to induce production of oxidative stress biomarkers. Introducing 2,2':6',2″-terpyridine ligands provoked the smallest changes in antioxidant enzymes activity, lipid peroxidation, and expression of heme oxygenase-1, that undoubtedly indicated that this complex had the lowest impact on redox status in heart tissue. These findings may be useful in synthesis of novel platinum analogues with lower potential for oxidative stress induction. However, the fact that platinum complexes could induce toxic effects in the heart by other mechanisms should be taken into the consideration.

Platinum Complexes-Induced Cardiotoxicity of Isolated, Perfused Rat Heart: Comparison of Pt(II) and Pt(IV) Analogues Versus Cisplatin.

We have compared the cardiotoxicity of five platinum complexes in a model of isolated rat heart using the Langendorff technique. These effects were assessed via coronary flow (CF) and cardiac functional parameters. cis-Diamminedichloroplatinum(II) (cisplatin, CDDP), dichloro-(1,2-diaminocyclohexane)platinum(II) (Pt((II))DACHCl2), dichloro-(ethylenediamine)platinum(II) (Pt((II))ENCl2), tetrachloro-(1,2-diaminocyclohexane)platinum(IV) (Pt((IV))DACHCl4) and tetrachloro-(ethylenediamine)platinum(IV) (Pt((II))ENCl4) were perfused at increasing concentrations of 10(-8), 10(-7), 10(-6), 10(-5) and 10(-4) M during 30 min. In this paper, we report that cisplatin-induced dose-dependent effects on cardiac contractility and coronary flow both manifested as decrease in cardiac contractile force (dP/dt)max, heart rate and significant reduction in CF. Pt((II))ENCl2, Pt((IV))ENCl2 and Pt((IV))DACHCl4 did induce dose-dependent response only in case of CF. Our results could be also important for better understanding dose-dependent side effects of potential metal-based anticancer drugs.

Neonatal screening of hearing function by otoacustic emissions--a single center experience.

BACKGROUND/AIM: Nowadays development of techniques enables detection of hearing impairment in a very short time, immediately after birth by using otoacoustic emissions. They are low-pitched sounds produced in physiologically clear cochlea and can be recorded in cochlear outer meatus. By this method, complete data are found on a whole presynaptic auditory nervous system functioning that has mostly been affected by pathological changes making it a perfect screening test. Reliability and sensibility of this method is up to 98%. The aim of this study was to present the first results of systematic neonatal screening of hearing function by otoacoustic emissions in the Clinical Center Kragujevac (Kragujevac, Serbia). METHODS: This prospective study of neonatal hearing screening function, initiated systematically by the 2008 at the Clinical Center Kragujevac, included full-term newborns and premature born ones, within the first 24 h after birth, using a DPOAEs interacoustics otoread-screener. Retesting was done after a month. RESULTS: From January 1st, 2009 to December 1st, 2010, a total number of examined infants by this method was 1,994 out of which 1,778 were full-term and 216 were premature born. The test passing was higher in the group of full-term babies (92.5%) than in the preterm ones (55.1%). No bilateral answers were recorded in premature born children compared to the full-term ones, of whom a larger number was with missing lateral responses. The results of re-examination test in the group of full-term born and premature newborns were 83.7%, and 61%, respectively. CONCLUSION: Deliberately provoked transient otoacoustic emission is an efficient method in testing hearing function in newborns, since it is non-invasive, rapid and objective. Its correlation with audibly evoked potentials is very high, which confirms its reliability.

[Condition of hearing sense and tinnitus before and after the treatment of otosclerosis].

INTRODUCTION: Otosclerosis is an osteodystrophy disease of the bony labyrinth of the ear which leads to stapes fixation and to bradyecoia of a conductive type. The microsurgical treatment by the use of a stapes prosthesis provides hearing improvement and a reduction or disappearing of tinnitus. The aim of our study was to determine the hearing condition and tinnitus before and after the treatment of otosclerosis. MATERIAL AND METHODS: A hundred patients with otosclerosis, aged 20 to 70, were surgically treated at the Otorhinolaryngology Clinic and the Functional Diagnostics, Military Medical Academy, Belgrade. After the treatment, the audiometric examinations were performed in order to assess the hearing condition and tinnitus was assessed by a questionnaire. The subjective assessment of tinnitus was ranged as present, reduced or absent. RESULTS: Before the treatment, hearing impairment was present in all the patients, while tinnitus was found in 91% of them. One year following the surgical treatment hearing improvement was found in 96% of the patients, and tinnitus cessation in 89% of them. CONCLUSION: The surgical treatment can result in hearing improvement and cessation or reduction of tinnitus.

[The use of combined hyperbaric oxygenation and erythropoietin in the treatment of cardiac insufficiency].

INTRODUCTION: The aim of this research is to evaluate therapy efficiacy of hyperbaric oxgenation (HBO) with regenerative effects on human tissues and erythropoietin, as a nonspecific growth factor. MATERIAL AND METHODS: This study included a group of 9 patients with echocardiographically diagnosed cardiac insufficiency with ejection firaction (EF%) under 60%. HBO was used according to the protocol for patients with severe cardiac insufficiency (a total of 15 treatments). All patients also received subcutaneous erythropoietin, 2000 i.v., every other day. Control echocardiography was done 30-45 days after they finished their treatments. RESULTS: The average ejection fraction before treatment was 46%. After treatment, the average EF% was 57%, so it increased by 11%. All patients felt subjectively better, with improved capacity to physical efforts. DISCUSSION AND CONCLUSION: Ejection fraction of 30-40% is an indication for hyperbaric oxygenation therapy. The decision about the treatment is made by the physician based on his experience, general condition of the patient, frequency and severity of hypoxic episodes. If EF% is 30% or below, HBO is not recommended, because antioxidative defense mechanisms are exhausted under hyypoxia and the balance of the organism should not be changed. An increase in average EF% by 11% demonstrates that combined use of HBO and Erythropoietin gives good results.