Search

Chronic heart failure and obesity are two conditions which despite all the advances made in the recent years, still represent two of the leading causes of morbidity and mortality worldwide. Moreover, a well-known fact is that the risk of sudden cardiac death, mostly related to malignant arrhythmias is higher in apparently healthy obese individuals in comparison with lean subjects. On the other hand, obese heart failure patients bring unique challenges in the diagnosis of heart failure, having a better prognosis than their normal or underweight counterparts. Taking into account the above-mentioned existing data, there are questions regarding whether cardiac arrhythmias such as atrial fibrillation or ventricular arrhythmias in this population have certain evolutive particularities. This paper describes various mechanisms of cardiac arrhythmias found in obese heart failure patients, such as myocardial architectural changes, neurohormonal and paracrine modifications.

There are limited neuroprotective strategies for various central nervous system conditions in which fast and sustained management is essential. Neuroprotection-based therapeutics have become an intensively researched topic in the neuroscience field, with multiple novel promising agents, from natural products to mesenchymal stem cells, homing peptides, and nanoparticles-mediated agents, all aiming to significantly provide neuroprotection in experimental and clinical studies. Dexmedetomidine (DEX), an α2 agonist commonly used as an anesthetic adjuvant for sedation and as an opioid-sparing medication, stands out in this context due to its well-established neuroprotective effects. Emerging evidence from preclinical and clinical studies suggested that DEX could be used to protect against cerebral ischemia, traumatic brain injury (TBI), spinal cord injury, neurodegenerative diseases, and postoperative cognitive disorders. MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level, inhibiting the translation of mRNA into functional proteins. In vivo and in vitro studies deciphered brain-related miRNAs and dysregulated miRNA profiles after several brain disorders, including TBI, ischemic stroke, Alzheimer’s disease, and multiple sclerosis, providing emerging new perspectives in neuroprotective therapy by modulating these miRNAs. Experimental studies revealed that some of the neuroprotective effects of DEX are mediated by various miRNAs, counteracting multiple mechanisms in several disease models, such as lipopolysaccharides induced neuroinflammation, β-amyloid induced dysfunction, brain ischemic-reperfusion injury, and anesthesia-induced neurotoxicity models. This review aims to outline the neuroprotective mechanisms of DEX in brain disorders by modulating miRNAs. We address the neuroprotective effects of DEX by targeting miRNAs in modulating ischemic brain injury, ameliorating the neurotoxicity of anesthetics, reducing postoperative cognitive dysfunction, and improving the effects of neurodegenerative diseases.

Cerebral ischemia reperfusion injury is a debilitating medical condition, currently with only a limited amount of therapies aimed at protecting the cerebral parenchyma. Micro RNAs (miRNAs) are small, non-coding RNA molecules that via the RNA-induced silencing complex either degrade or prevent target messenger RNAs from being translated and thus, can modulate the synthesis of target proteins. In the neurological field, miRNAs have been evaluated as potential regulators in brain development processes and pathological events. Following ischemic hypoxic stress, the cellular and molecular events initiated dysregulate different miRNAs, responsible for long-terming progression and extension of neuronal damage. Because of their ability to regulate the synthesis of target proteins, miRNAs emerge as a possible therapeutic strategy in limiting the neuronal damage following a cerebral ischemic event. This review aims to summarize the recent literature evidence of the miRNAs involved in signaling and modulating cerebral ischemia-reperfusion injuries, thus pointing their potential in limiting neuronal damage and repair mechanisms. An in-depth overview of the molecular pathways involved in ischemia reperfusion injury and the involvement of specific miRNAs, could provide future perspectives in the development of neuroprotective agents targeting these specific miRNAs.

Objectives: This study focuses on the assessment of attitudes and practices regarding research among undergraduate medical students from Cluj-Napoca, Romania. Material and Methods: A cross-sectional study was performed thorough anonymous questionnaires (May–June 2018) among 510 third- and fifth-year students of Iuliu Hatieganu University of Medicine and Pharmacy from Cluj-Napoca, Romania. Results: More than 60% of the third- and fifth-year students declared that they were interested and willing to perform research during medical studies, while more than two-thirds were interested in doing so after graduation. In total, 6% of third-year students and 31% of fifth-year students declared that they had prepared a scientific presentation for a medical congress at least once. Around 9% of the third-year students contributed to the writing of a scientific article and participated in research projects. Among fifth-year students, one-quarter were involved in writing scientific papers, and 21% participated in research projects. Conclusions: To the best of our knowledge, this study assesses, for the first time in Romania, the perspectives and behaviors of medical undergraduate students with regard to involvement in research activities. The results show that Romanian medical students value opportunities for conducting research, which encourages institutional initiatives that support their involvement in curricular and extracurricular research activities.

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.

Sensorineural hearing loss is a prevailing health issue worldwide which usually occurs due to sensory inner ear cell destruction. These cells, once damaged, do not regenerate in mammals resulting in permanent hearing loss. Effective treatment of inner ear diseases is strongly correlated with efficient drug delivery to the inner ear. Researchers have made important efforts to deliver drugs locally to the inner ear in a safe and controllable manner. Different strategies and drug delivery systems were used to mitigate the resistance exerted by the multiple anatomical barriers found in the inner ear. Nanoparticles represent an option for sustained drug delivery to the inner ear. Nanocarrier-based systems can diffuse through the round and oval window membrane allowing for direct delivery into the inner ear components. Certain types of enhanced nanoparticles can focus on specific parts of the inner ear, providing targeted delivery which might represent the future therapy for sensorineural hearing loss. In this article, we will present the latest advances in the treatment of hearing loss based on nanoparticles.

Aim: The present study analyzed clinical and biological factors that might predict achievement of tolerance in patients with IgE-mediated cow milk allergy (CMA). Method: Seventy patients with IgE-mediated CMA (44.24 ± 24.16 months) were included in the study. The patients were evaluated clinically through skin prick test and sIgE to whole milk, casein, beta-lactoglobulin and alpha-lactalbumin. An eviction diet of 6 months was established, followed by oral food challenge test (OFC) and oral immunotherapy (OIT) with baked milk for 6 months. The tolerance was assessed after 2 years follow up. Results: Thirty percent of patients presented anaphylaxis of different degrees of severity as first manifestation of CMA. Sixty-two patients followed OIT or an accelerated reintroduction of milk. Ten patients (14.28%) did not obtain tolerance to milk within 2 years. A larger wheal in SPT and higher sIgE to milk, casein and betalactoglobulin were noted in patients with positive OFC. A basal level of

Atherosclerotic cardiovascular disease is the most common cause of morbidity and mortality worldwide. Diabetes mellitus increases cardiovascular risk. Heart failure and atrial fibrillation are associated comorbidities that share the main cardiovascular risk factors. The use of incretin-based therapies promoted the idea that activation of alternative signaling pathways is effective in reducing the risk of atherosclerosis and heart failure. Gut-derived molecules, gut hormones, and gut microbiota metabolites showed both positive and detrimental effects in cardiometabolic disorders. Although inflammation plays a key role in cardiometabolic disorders, additional intracellular signaling pathways are involved and could explain the observed effects. Revealing the involved molecular mechanisms could provide novel therapeutic strategies and a better understanding of the relationship between the gut, metabolic syndrome, and cardiovascular diseases.

Grape pomace and grape seeds, by-products of the wine industry, and grapevine cane resulting from grapevine pruning are cheap matrices containing important amounts of polyphenols. While there is a continuous need of introducing new ways of these by-products valorization, we propose their use as a source of bioactive polyphenols for complementary therapy in ischemic heart diseases. As oxidative stress plays an important role in these diseases, by their antioxidant/pro-oxidant properties, these compounds, mainly flavan-3-ols, procyanidins, and resveratrol may counteract the damage of the oxidative stress. For instance, to some extent, the grape seed extract, considered as an antioxidant nutritive supplement, may have pro-oxidant activity as well, depending on dose, duration of administration, and other dietary components.In vitrostudies confirm that the antioxidant activity of this extract might be mediated by pro-oxidanto-quinones and oxidation products of the polyphenols from grape and winery byproducts, indicating that quinones, as oxidation products, are involved in the modulation of the antioxidant/pro-oxidant balance at the cellular level in the case of catechin-type compounds, in the absence or presence of oxidative stress inducers.In vivo, studies indicate that a grape pomace-rich diet results in a significant increase of the total antioxidant status in the plasma, liver, spleen, and kidneys. Also, the administration of grape pomace shows antioxidant activity with positive effects on health. In this context, the present review aims to present the most recent research focused on the antioxidant/pro-oxidant actions of the bioactive polyphenols from grapevine and wine byproducts, in conditions of ischemic heart diseases as assessedin vitroorin vivo.

Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Paraoxonase-1 (PON1), circulates in blood bound to high-density lipoproteins and reduces systemic oxidative stress. The aim of this study was to evaluate PON1 serum concentration and PON1 arylesterase activity (AREase) in patients with AF. We studied a group of 67 patients with symptomatic paroxysmal or persistent AF admitted for cardioversion and a control group of 59 patients without AF. Clinical parameters, lipid profile, PON1 concentration and AREase were evaluated. A significant difference in serum PON1 concentration and in AREase was found among the two groups. In a multivariate linear regression model, the presence of AF was associated with low PON1 concentration (P = .022). The body mass index was also independently associated with PON1 values (P .001). Only the high-density lipoproteins-cholesterol level was independently associated with AREase (P = .002). PON1 serum concentrations and AREase were diminished in patients with AF, and the presence of AF was independently associated with low PON1 values.

There are multiple concerns associated with methotrexate (MTX), widely recognized for anti-neoplastic and anti-inflammatory effects in life-threatening disease conditions, i.e., acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, psoriasis, and rheumatoid arthritis, due to long-term side effects and associated toxicity, which limits its valuable potential. MTX acts as an inhibitor of dihydrofolate reductase, leading to suppression of purine and pyrimidine synthesis in high metabolic and turnover cells, targeting cancer and dysregulated immune cells. Due to low discrimination between neoplastic cells and naturally high turnover cells, MTX is prone to inhibiting the division of all fast-dividing cells, causing toxicity in multiple organs. Nutraceutical compounds are plant-based or food-derived compounds, used for their preventive and therapeutic role, ascertained in multiple organ dysfunctions, including cardiovascular disease, ischemic stroke, cancer, and neurodegenerative diseases. Gut microbiota and microbiota-derived metabolites take part in multiple physiological processes, their dysregulation being involved in disease pathogenesis. Modulation of gut microbiota by using nutraceutical compounds represents a promising therapeutic direction to restore intestinal dysfunction associated with MTX treatment. In this review, we address the main organ dysfunctions induced by MTX treatment, and modulations of them by using nutraceutical compounds. Moreover, we revealed the protective mechanisms of nutraceuticals in MTX-induced intestinal dysfunctions by modulation of gut microbiota.

Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most widely used drugs due to their anti-inflammatory, analgesic and antipyretic pharmacological effects. Gastrointestinal side effects are some of the most severe and frequent side effects of NSAIDs. These depend on the balance of the gut microbiome, the abundance of Gram-negative bacteria, and the amount of lipopolysaccharide released. Therefore, restoring or improving gut bacteria balance with probiotic supplements could prove to be an adjuvant therapy against mild NSAID-induced enteropathy. Twenty-five Wistar albino male rats were divided into five groups. The negative control group was administered carboxymethylcellulose and the positive control group diclofenac (DIC), 8 mg/kg for 7 days, which represented the enteropathy model. Treatment groups consisted of a combination of pro-biotic spores (MSB), amino acids and immunoglobulins supplement (MM), which were also administered for 7 days. We analyzed hepatic injury markers (AST, ALT) and creatinine, and inflammatory markers, IL-6, TNF-α, PGE2, iNOS, as well as total antioxidant capacity. The results obtained in the present study suggest that the modulation of the intestinal microbiota by administration of probiotics (Bacillus spores), alone or in combination with immunoglobulins and amino acids, represents an attractive therapy for the prevention of NSAID-induced enteropathy.

Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) remains a challenging issue. This study aims to explore the left atrial appendage function by transesophageal echocardiography (TEE) and assess its value in predicting AF recurrence following RFCA in paroxysmal AF patients. Eighty-one patients with paroxysmal AF that underwent RFCA were recruited. TEE was performed before ablation with the assessment of left atrial appendage emptying flow velocity (LAAeV). AF recurrence occurred in 24 patients (29.6%) within 12 months after RFCA. The left atrium diameter (LAD) and left atrium volume index (LAVI) were both significantly higher in the recurrence group compared to the non-recurrence group, while the LAAeV was significantly lower in the recurrence group. LAD, LAVi and LAAeV were univariately significant risk factors for AF recurrence after ablation. Based on receiver operating curve (ROC), LAAeV < 40.5 cm/s, LAVi > 40.5 mL and LAD > 41 mm were identified as cut-off values for predicting AF recurrence. In multivariate regression analysis LAAeV < 40.5 cm/s (HR 8.194, 95% CI 2.980–22.530, p < 0.001) was identified as the only statistically significant independent predictor of AF recurrence, as the statistical significance threshold was not achieved for LAVI > 40.5 mL and LAD > 41 mm (p = 0.319; p = 0.507, respectively). A low LAAeV was the only important independent predictor of AF recurrence within 1 year after first RFCA.

Obesity and Overweight have the highest rate of incidence and prevalence in the past 3 decades, as global pathologies. The purpose of this study was to evaluate cardiovascular, classic and modern risk factors in overweight and obese patients by studying lipid metabolism (total cholesterol, HDL-cholesterol, non-HDL-cholesterol, LDL-cholesterol, serum triglycerides), glucose metabolism, insulin resistance and insulin sensitivity, the prevalence of hypertension (HBP) and the prevalence of metabolic syndrome (MS). This analytical study was performed on 111 subjects divided as follows: Group I consisting of 27 normal weight subjects - NW; Group II consisting of 84 overweight and obese subjects - OW + O: 36 overweight patients - OW; 33 patients with grade I obesity - O-I; 13 patients with grade II obesity - O-II; 2 patients with grade III obesity - O-III. The overweight and obese, although unknown with heart disease, have significant metabolic changes, such as atherogenic dyslipidemia, dysglycemia, high insulin resistance and low insulin sensitivity, metabolic syndrome, these being the first steps towards endothelial dysfunction and early atherosclerosis.

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers

Asthma is defined by The Initiative for Asthma (GINA 2018) as a heterogeneous disease, which include chronic airway inflammation and a history of respiratory symptoms. In the last decades asthma had a rise in prevalence, becoming one of the most frequent diagnosed diseases in the world. The main goals of asthma management are to achieve good symptom control, minimize the risks of exacerbations, decrease rescue medication intake, improve the quality of life by decreasing respiratory system inflammation and ameliorating the patient’s lung function. Beside effective medications, asthma continues to impair quality of life for most patients. Due to the difficulty of controlling symptoms and exacerbations, the need of developing complementary options of treatment is increasing in order to achieve an optimum control and a lower risk of acute episodes or fatal events. Pulmonary rehabilitation is suggested for asthma patients when adequate medical therapy poorly control the symptoms and mental, physical or social consequences of illness persist during the daily life. The following non-drug therapy components are included in the rehabilitation program: physical training, comprehensive smoking cessation program, comprehensive patient education, respiratory physiotherapy, psychosocial support and comprehensive nutritional counseling. These complementary therapies have been proven to improve muscle strength, exercise capacity and symptomatology. Also, it has been associated to fewer exacerbations and a lower use of rescue medication, leading to a better quality of life. Key words: asthma, quality of life, symptomatology, rehabilitation, physiotherapy

Heart failure continues to be a major worldwide medical issue, associated with high morbidity and mortality. The need for ideal biomarkers to aid the diagnosis and prognosis in certain situations, such as obesity or atrial fibrillation is still ongoing. Obese patients are commonly hyperleptinemic. The aim of the study is to assess the role of several biomarkers in overweight and obese patients diagnosed with heart failure, depending on the presence or absence of atrial fibrillation and also their relationship with leptin. The study included 88 overweight and obese patients, with a body mass index (BMI) ≥25 kg/m2, admitted for worsening heart failure. Of these, 52.2% had atrial fibrillation. Dosage of NT-proBNP was performed using the chemiluminescence method. MR-proANP, galectin-3 and leptin were dosed using the ELISA method. A value of P [0.05 was defined as statistically significant. The values of natriuretic peptides NT-proBNP and MR-proANP were significantly increased. Only NT-proBNP was significantly influenced by renal function. No statistically significant correlation was found between heart failure-specific biomarkers and leptin secretion. There were no significant differences in the biomarkers levels between the 2 groups of patients. No statistically significant correlation was found between heart failure-specific biomarkers and leptin secretion. Obese patients with heart failure had significantly increased values of all the studied parameters, but the presence of atrial fibrillation did not influence their levels. High leptin levels were not directly correlated with the levels of heart failure-specific biomarkers.

In those countries where education and smoking prevention campaigns are carried out at school level, there has been a decline in the prevalence of smoking among pupils. Nicotine addiction represents a sum of pharmacological, electrophysiological and molecular genetic mechanisms and behavior patterns. The study was conducted from December 2016, to July 2017 and it consisted in an online survey posted on a website. The participants accessed the survey through an e mail link. The study population consisted of 1144 teachers (from primary school, gymnasium and college). The declared percentage of daily smokers was 14%, below the European average, while 20.5% were declared ex-smokers, 11.2% were occasional smokers and 54.4% never smoked. The theme of smoking was approached by 79.2% of teachers during conducting classes and 81.6% of them advised smokers to stop smoking. Teachers can influence the pupils� behavior by personal example and by teaching, inside and outside the school, thus preventing nicotine addiction. Decreasing the prevalence of smoking among teachers will inevitably lead in the future to a decrease of adolescent smokers� incidence. Our study was a pilot project that can draw important directions in educational and preventive campaigns in schools.

The ability of Berberis vulgaris bark extract (BVE) to improve the lipid profile was evaluated in an experimental model of dyslipidemia, along with its effects on liver and kidney functions. Fifty rats divided into five groups of ten animals each were fed with normal or lard-based diet and orally treated with 0.9% saline solution, atorvastatin (2.5 mg/kg per body weight) or extract of BVE (300 and 500 mg/kg/day) for eight weeks. Lipid profile, liver and renal functions were assessed in normal and diet-induced hypercholesterolemic rats. The results were compared between the groups treated with Berberis extract and the group without treatment, respectively that one treated with the standard drug (atorvastatin). Administration of BVE or atorvastatin significantly decreases the elevated serum lipid profile (p [0.05). The extract also protects against dyslipidemia-induced non-alcoholic fatty liver disease (NAFLD). The activities of the plant extract are dose dependent and it compares favorably with the standard drug atorvastatin. Variations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and urea level measurements were neither different between the two determinations nor between groups, but creatinine values decreased in rats in the BVE or atorvastatin-treated groups. The findings of the current study have suggested that BVE intake suppresses the accumulation of hepatic lipids and lipid parameters and reduce the risk of NAFLD. So, BVE can be useful in hypercholesterolemia.

The overlap syndrome (OS) is defined as a synergic relation between obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). Patients with overlap syndrome present the clinical features of each disorder to a greater or a lesser extend depending on the predominant disease. We assessed the main differences between patients with OS and patients with OSA and we highlight the importance of nocturnal hypoxemia on clinical status and management of the patients with overlap syndrome, in order to simplify OSA screening tests in patients with COPD. The study population included 62 selected patients divided in two groups: the first group � subjects diagnosed with OS and the second group - subjects with OSA, without the diagnostic of COPD. The majority of the patients were male, with a mean age of 55�9.84 years in the OSA group and 65.5�10.32 years in the OS group. The nocturnal hypoxemia was more important in the OS grup, with 276.83 minutes spent at a SpO2 below 90% versus 132.98 minutes in the OSA group. The mean AHI was 57.7�29.244 events/hour of sleep in the OS group and 50.7�26.01 events/hour of sleep in the OSA group. At the diagnosis, the mean daytime SpO2 was 90.9�3.59% in the OS group and 95.9�1.57 % in the OSA group. There were statistically significant differences between the two groups concerning age, AHI, Epworth Slepiness Scale, nocturnal desaturation, medium and minimum SpO2 during sleep, daytime SpO2 at the diagnosis and at 1-year follow-up, the presence of cardiovascular comorbidities such as pulmonary hypertension and heart failure. Our study showed that patients with COPD have OSA predictors that differ from those usually recognise in the general population. In OS patients, the most important parameter is the nocturnal hypoxemia. So, it is very useful that the clinicians be trained to include in the management of selected obese COPD patients, comprehensive sleep history, sleep hygiene and OSA screening because, in clinical practice, OSA is quite often underdiagnosed in these patients.

Background: During the last years, the COVID-19 pandemic meets the pandemic generated by obesity, raising many questions regarding the outcomes of those with severe forms of infection. Methods: The present systematic review summarises and analyses the data providing evidence for or against the “obesity-paradox” in COVID-19 patients. After applying the inclusion and exclusion criteria, 23 studies were included. We also analysed the presumably underlying basic mechanisms. Results: The patients with a body mass index (BMI) of 30–40 kg/m2 presented severe symptoms that led to intensive care unit (ICU) admission but not increased death rate. Those with a higher degree of obesity, with a BMI higher than 40 kg/m2, led to a rise in the death rate, particularly in young patients. Obesity was associated with a higher rate of ICU admission but was not determined as an independent predictor of increased mortality. In contrast, some studies suggest a strong association between obesity or morbid obesity and the risk of death. Conclusions: The existence of “obesity-paradox” cannot be stated; our study presents obesity as a critical risk factor in the evolution of COVID-19.

The objectives of this study were to investigate the cardio-protective, hepatoprotective and nephroprotective effects of curcumin nanoparticle (NC) pretreatment compared to conventional curcumin (CC) on acute myocardial infarction (AMI) in rats with type 1 diabetes mellitus (T1DM). Fifty-six Wister Bratislava rats were divided into eight groups. The first four groups—C (control group), AMI (group with AMI), T1DM (group with T1DM), and T1DM-AMI (group with T1DM and AMI)—received only saline (S) during the whole experiment. Two groups—S-T1DM-CC-AMI and S-T1DM-NC-AMI—were pretreated with S before T1DM induction. The S-T1DM-CC-AMI group received CC (200 mg/Kg bw (bw—body weight)) after T1DM induction, while the S-T1DM-NC-AMI group received NC (200 mg/Kg bw) after T1DM induction. the CC-T1DM-CC-AMI group received CC (200 mg/Kg bw) during the whole experiment. Similarly, the NC-T1DM-NC-AMI group received NC (200 mg/Kg bw) over the entire experiment. T1DM was induced on day 7 using a single dose of streptozotocin (STZ). AMI was induced with isoproterenol (ISO) on day 22. Both curcumin formulations, CC and NC, prevented the following electrocardiographic changes: prolongation of the QRS complex, enlargement of QT and QTc intervals, and ST-segment elevation. Glucose levels and lipid profile parameters were reduced up to 1.9 times, while C-peptide serum levels were increased up to 1.6 times in groups that received CC or NC. Liver function parameters (aspartate transaminase, alanine transaminase) and kidney function parameters (creatinine, urea) were reduced 4.8 times, and histological changes of liver and kidney tissue were improved by CC or NC administration. Pretreatment with NC proved significantly higher cardioprotective, hepatoprotective and nephroprotective effects in the case of AMI in T1DM.

Cardiotoxicity is a well-recognised side effect of cancer-related therapies with a great impact on outcomes and quality of life in the cancer survivor population. The pathogenesis of chemotherapy-induced cardiotoxicity in patients with gastrointestinal cancers involves various molecular mechanisms, and the combined use of various chemotherapies augments the risk of each drug used alone. In terms of cardiotoxicity diagnosis, novel biomarkers, such as troponins, brain natriuretic peptide (BNP), myeloperoxidases and miRNAs have been recently assessed. Echocardiography is a noninvasive imaging method of choice for the primary assessment of chemotherapy-treated patients to generally evaluate the cardiovascular impact of these drugs. Novel echocardiography techniques, like three-dimensional and stress echocardiography, will improve diagnosis efficacy. Cardiac magnetic resonance (CMR) can evaluate cardiac morphology, function and wall structure. Corroborated data have shown the importance of CMR in the early evaluation of patients with gastrointestinal cancers, treated with anticancer drugs, but further studies are required to improve risk stratification in these patients. In this article, we review some important aspects concerning the cardiotoxicity of antineoplastic drugs used in gastrointestinal cancers. We also discuss the mechanism of cardiotoxicity, the role of biomarkers and the imaging methods used in its detection.

The study’s aim was to characterize the composition of Nigella sativa seed (NSO) and grape seed (GSO) oils, and to evaluate their cardioprotective and anti-inflammatory effect on isoproterenol (ISO)-induced ischemia in rats. Materials and Methods: NSO and GSO supplements were physicochemically characterized. Liquid chromatography–mass spectrometry (HPLC-MS), Fourier-transform infrared spectroscopy (FTIR), and gas chromatography–mass spectrometry (GC-MS) analyses were used to determine the phytochemical composition in the oils. Total polyphenol content (TPC) and in vitro antioxidant activity were also determined. Pretreatment with 4 mL/kg/day NSO or GSO was administered to rats for 14 days. The experimental ischemia was induced by a single administration of ISO 45 mg/kg after 14 days. An electrocardiogram (ECG) was performed initially and 24 h after ISO. Biological evaluation was done at the end of experiment. Results: The HPLC-MS, GC-MS, and FTIR analyses showed that both NSO and GSO are important sources of bioactive compounds, especially catechin and phenolic acids in GSO, while NSO was enriched in flavonoids and thymol derivatives. Pretreatment with GSO and NSO significantly reduced ventricular conduction, prevented the cardiotoxic effect of ISO in ventricular myocardium, and reduced the level of proinflammatory cytokines and CK-Mb. Conclusion: Both NSO and GSO were shown to have an anti-inflammatory and cardioprotective effect in ISO-induced ischemia.

Background: Health policies in transitioning health systems are rarely informed by the economic burden of disease due to scanty access to data. This study aimed to estimate direct and indirect costs for first-ever acute ischemic stroke (AIS) during the first year for patients residing in Cluj, Romania, and hospitalized in 2019 at the County Emergency Hospital (CEH). Methods: The study was conducted using a mixed, retrospective costing methodology from a societal perspective to measure the cost of first-ever AIS in the first year after onset. Patient pathways for AIS were reconstructed to aid in mapping inpatient and outpatient cost items. We used anonymized administrative and clinical data at the hospital level and publicly available databases. Results: The average cost per patient in the first year after stroke onset was RON 25,297.83 (EUR 5226.82), out of which 80.87% were direct costs. The total cost in Cluj, Romania in 2019 was RON 17,455,502.7 (EUR 3,606,505.8). Conclusions: Our costing exercise uncovered shortcomings of stroke management in Romania, particularly related to acute care and neurorehabilitation service provision. Romania spends significantly less on healthcare than other countries (5.5% of GDP vs. 9.8% European Union average), exposing stroke survivors to a disproportionately high risk for preventable and treatable post-stroke disability.

Heart failure is still the leading cause of hospitalization in patients over 65 years of age and is defined as a multifactorial pathology which involves environmental factors and also genetic predispositions. The aim of the present study was to evaluate a possible correlation between single nucleotide polymorphisms (SNPs) of angiotensin converting enzyme 2 (ACE2) and monocyte chemoattractant protein-1 (MCP-1) genes and cardiac remodeling in Caucasian patients diagnosed with heart failure. Our comparative translational research study included 116 patients diagnosed with heart failure and was carried out in Cluj-Napoca, Romania between September 2017 and March 2019. Three SNPs, namely rs4646156, rs4646174 and rs1024611, were genotyped using a Taqman real-time PCR technique. Our results showed that carriers of the AA genotype for ACE2 rs4646156 had a significant dilatation of the left ventricle (LV) with signs of LV hypertrophy (LVH), while TT carriers had a significant left atrial dilatation. For ACE2 rs4646174, homozygotes for the C allele presented a dilated LV with signs of LVH with statistical significance and had a tendency towards a lower ejection fraction. MCP-1 rs1024611 AA variant carriers had a significant LVH in the dominant model. In conclusion, our study showed a strong association between echocardiographic parameters of cardiac remodeling and SNPs rs4646156, rs4646174 of ACE2 and rs1024611 of MCP-1.

N-Pep-12 is a dietary supplement with neuroprotective and pro-cognitive effects, as shown in experimental models and clinical studies on patients after ischemic stroke. We tested the hypothesis that N-Pep-12 influences quantitative electroencephalography (QEEG) parameters in patients with subacute to chronic supratentorial ischemic lesions. We performed secondary data analysis on an exploratory clinical trial (ISRCTN10702895), assessing the efficacy and safety of 90 days of once-daily treatment with 90 mg N-Pep-12 on neurocognitive function and neurorecovery outcome in patients with post-stroke cognitive impairment against a control group. All participants performed two 32-channel QEEG in resting and active states at baseline (30–120 days after stroke) and 90 days later. Power spectral density on the alpha, beta, theta, delta frequency bands, delta/alpha power ratio (DAR), and (delta+theta)/(alpha+beta) ratio (DTABR) were computed and compared across study groups using means comparison and descriptive methods. Secondarily, associations between QEEG parameters and available neuropsychological tests were explored. Our analysis showed a statistically significant main effect of EEG segments (p

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The aim of this study was to evaluate the possible association between paraoxonase-1 (PON1), periostin (POSTN), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 serum concentration with non-invasive liver fibrosis scores, in a cohort of patients with NAFLD. We studied a cohort of 52 patients diagnosed with NAFLD. The NAFLD fibrosis score (NFS), Fibrosis-4 Index (FIB-4), AST to platelet ratio index (APRI) and BARD scores were calculated for each patient. We determined the PON1, POSTN, TNF-α, IL-6, and IL-10 serum values using ELISA kits. There was no correlation between PON1 or POSTN serum levels and non-invasive liver fibrosis. The TNF-α serum values were independently associated with the liver fibrosis scores (P=0.02 for NFS and P=0.002 for FIB-4). Age and metabolic syndrome were also independently linked to the fibrosis scores. In conclusion, serum levels of TNF-α, age and metabolic syndrome were associated with the non-invasive liver fibrosis scores.

Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224N results in profound progressive functional deficit, memory impairment and brain pathology from 5h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.

Military personnel are often exposed to high environmental heat associated with industrial or ambient abundance of nanoparticles (NPs) affecting brain function. We have shown that engineered metal NPs Ag and Cu exacerbate hyperthermia induced brain pathology. Thus, exploration of novel drug therapy is needed for effective neuroprotection in heat stroke intoxicated with NPs. In this investigation neuroprotective effects of cerebrolysin, a balanced composition of several neurotrophic factors and active peptides fragments exhibiting powerful antioxidant and anti-ischemic effects was examined in heat stroke after NPs intoxication. In addition, its efficacy is compared to currently used drugs in post-stroke therapies in clinics. Thus, levertiracetam, pregabalin, topiramat and valproate were compared in standard doses with cerebrolysin in heat stroke intoxicated with Cu or Ag NPs (50-60nm, 50mg/kg, i.p./day for 7 days). Rats were subjected to 4h heat stress (HS) in a biological oxygen demand incubator at 38°C (Relative Humidity 45-47%; Wind velocity 22.4-25.6cm/s) that resulted in profound increase in oxidants Luminol, Lucigenin, Malondialdehyde and Myeloperoxidase, and a marked decrease in antioxidant Glutathione. At this time severe reductions in the cerebral blood flow (CBF) was seen together with increased blood-brain barrier (BBB) breakdown and brain edema formation. These pathophysiological responses were exacerbated in NPs treated heat-stressed animals. Pretreatment with cerebrolysin (2.5mL/kg, i.v.) once daily for 3 days significantly attenuated the oxidative stress, BBB breakdown and brain edema and improved CBF in the heat stressed group. The other drugs were least effective on brain pathology following heat stroke. However, in NPs treated heat stressed animals 5mL/kg conventional cerebrolysin and 2.5mL/kg nanowired cerebrolysin is needed to attenuate oxidative stress, BBB breakdown, brain edema and to improve CBF. Interestingly, the other drugs even in higher doses used are unable to alter brain pathologies in NPs and heat stress. These observations are the first to demonstrate that cerebrolysin is the most superior antioxidant and anti-ischemic drug in NPs exposed heat stroke, not reported earlier.

Spinal cord injury (SCI) is one of the leading causes of disability in Military personnel for which no suitable therapeutic strategies are available till today. Thus, exploration of novel therapeutic measures is highly needed to enhance the quality of life of SCI victims. Previously, topical application of BDNF and GDNF in combination over the injured spinal cord after 90 min induced marked neuroprotection. In present investigation, we added CNTF in combination with BDNF and/or GDNF treatment to examine weather the triple combination applied over the traumatic cord after 90 or 120 min could thwart cord pathology. Since neurotrophins attenuate nitric oxide (NO) production in SCI, the role of carbon monoxide (CO) production that is similar to NO in inducing cell injury was explored using immunohistochemistry of the constitutive isoform of enzyme hemeoxygenase-2 (HO-2). SCI inflicted over the right dorsal horn of the T10–11 segments by making an incision of 2 mm deep and 5 mm long upregulated the HO-2 immunostaining in the T9 and T12 segments after 5 h injury. These perifocal segments are associated with breakdown of the blood-spinal cord barrier (BSCB), edema development and cell injuries. Topical application of CNTF with BDNF and GDNF in combination (10 ng each) after 90 and 120 min over the injured spinal cord significantly attenuated the BSCB breakdown, edema formation, cell injury and overexpression of HO-2. These observations are the first to show that CNTF with BDNF and GDNF induced superior neuroprotection in SCI probably by downregulation of CO production, not reported earlier.

Military personnel often exposed to high summer heat are vulnerable to heat stroke (HS) resulting in abnormal brain function and mental anomalies. There are reasons to believe that leakage of the blood-brain barrier (BBB) due to hyperthermia and development of brain edema could result in brain pathology. Thus, exploration of suitable therapeutic strategies is needed to induce neuroprotection in HS. Extracts of Gingko Biloba (EGb-761) is traditionally used in a variety of mental disorders in Chinese traditional medicine since ages. In this chapter, effects of TiO2 nanowired EGb-761 and BN-52021 delivery to treat brain pathologies in HS is discussed based on our own investigations. We observed that TiO2 nanowired delivery of EGb-761 or TiO2 BN-52021 is able to attenuate more that 80% reduction in the brain pathology in HS as compared to conventional drug delivery. The functional outcome after HS is also significantly improved by nanowired delivery of EGb-761 and BN-52021. These observations are the first to suggest that nanowired delivery of EGb-761 and BN-52021 has superior therapeutic effects in HS not reported earlier. The clinical significance in relation to the military medicine is discussed.

Military personnel deployed in combat operations are highly prone to develop Parkinson's disease (PD) in later lives. PD largely involves dopaminergic pathways with hallmarks of increased alpha synuclein (ASNC), and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) precipitating brain pathology. However, increased histaminergic nerve fibers in substantia nigra pars Compacta (SNpc), striatum (STr) and caudate putamen (CP) associated with upregulation of Histamine H3 receptors and downregulation of H4 receptors in human cases of PD is observed in postmortem cases. These findings indicate that modulation of histamine H3 and H4 receptors and/or histaminergic transmission may induce neuroprotection in PD induced brain pathology. In this review effects of a potent histaminergic H3 receptor inverse agonist BF-2549 or clobenpropit (CLBPT) partial histamine H4 agonist with H3 receptor antagonist, in association with monoclonal anti-histamine antibodies (AHmAb) in PD brain pathology is discussed based on our own observations. Our investigation shows that chronic administration of conventional or TiO2 nanowired BF 2649 (1mg/kg, i.p.) or CLBPT (1mg/kg, i.p.) once daily for 1 week together with nanowired delivery of HAmAb (25μL) significantly thwarted ASNC and p-tau levels in the SNpC and STr and reduced PD induced brain pathology. These observations are the first to show the involvement of histamine receptors in PD and opens new avenues for the development of novel drug strategies in clinical strategies for PD, not reported earlier.

Military personnel are vulnerable to environmental or industrial exposure of engineered nanoparticles (NPs) from metals. Long-term exposure of NPs from various sources affect sensory-motor or cognitive brain functions. Thus, a possibility exists that chronic exposure of NPs affect blood-brain barrier (BBB) breakdown and brain pathology by inducing oxidative stress and/or nitric oxide production. This hypothesis was examined in the rat intoxicated with Ag, Cu or Al (50-60nm) nanoparticles (50mg/kg, i.p. once daily) for 7 days. In these NPs treated rats the BBB permeability, brain edema, neuronal nitric oxide synthase (nNOS) immunoreactivity and brain oxidants levels, e.g., myeloperoxidase (MP), malondialdehyde (MD) and glutathione (GT) was examined on the 8th day. Cu and Ag but not Al nanoparticles increased the MP and MD levels by twofold in the brain although, GT showed 50% decline. At this time increase in brain water content and BBB breakdown to protein tracers were seen in areas exhibiting nNOS positive neurons and cell injuries. Pretreatment with insulin like growth factor-1 (IGF-1) in high doses (1μg/kg, i.v. but not 0.5μg/kg daily for 7 days) together with NPs significantly reduced the oxidative stress, nNOS upregulation, BBB breakdown, edema formation and cell injuries. These novel observations demonstrate that (i) NPs depending on their metal constituent (Cu, Ag but not Al) induce oxidative stress and nNOS expression leading to BBB disruption, brain edema and cell damage, and (ii) IGF-1 depending on doses exerts powerful neuroprotection against nanoneurotoxicity, not reported earlier.

Military personnel are prone to traumatic brain injury (TBI) that is one of the risk factors in developing Alzheimer's disease (AD) at a later stage. TBI induces breakdown of the blood-brain barrier (BBB) to serum proteins into the brain and leads to extravasation of plasma amyloid beta peptide (ΑβP) into the brain fluid compartments causing AD brain pathology. Thus, there is a need to expand our knowledge on the role of TBI in AD. In addition, exploration of the novel roles of nanomedicine in AD and TBI for neuroprotection is the need of the hour. Since stem cells and neurotrophic factors play important roles in TBI and in AD, it is likely that nanodelivery of these agents exert superior neuroprotection in TBI induced exacerbation of AD brain pathology. In this review, these aspects are examined in details based on our own investigations in the light of current scientific literature in the field. Our observations show that TBI exacerbates AD brain pathology and TiO2 nanowired delivery of mesenchymal stem cells together with cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments, and monoclonal antibodies to amyloid beta protein thwarted the development of neuropathology following TBI in AD, not reported earlier.

Military personnel are often exposed to high altitude (HA, ca. 4500–5000 m) for combat operations associated with neurological dysfunctions. HA is a severe stressful situation and people frequently use methamphetamine (METH) or other psychostimulants to cope stress. Since military personnel are prone to different kinds of traumatic brain injury (TBI), in this review we discuss possible effects of METH on concussive head injury (CHI) at HA based on our own observations. METH exposure at HA exacerbates pathophysiology of CHI as compared to normobaric laboratory environment comparable to sea level. Increased blood-brain barrier (BBB) breakdown, edema formation and reductions in the cerebral blood flow (CBF) following CHI were exacerbated by METH intoxication at HA. Damage to cerebral microvasculature and expression of beta catenin was also exacerbated following CHI in METH treated group at HA. TiO2-nanowired delivery of H-290/51 (150 mg/kg, i.p.), a potent chain-breaking antioxidant significantly enhanced CBF and reduced BBB breakdown, edema formation, beta catenin expression and brain pathology in METH exposed rats after CHI at HA. These observations are the first to point out that METH exposure in CHI exacerbated brain pathology at HA and this appears to be related with greater production of oxidative stress induced brain pathology, not reported earlier.

Concussive head injury (CHI) often associated with military personnel, soccer players and related sports personnel leads to serious clinical situation causing lifetime disabilities. About 3-4k head injury per 100k populations are recorded in the United States since 2000-2014. The annual incidence of concussion has now reached to 1.2% of population in recent years. Thus, CHI inflicts a huge financial burden on the society for rehabilitation. Thus, new efforts are needed to explore novel therapeutic strategies to treat CHI cases to enhance quality of life of the victims. CHI is well known to alter endogenous balance of excitatory and inhibitory amino acid neurotransmitters in the central nervous system (CNS) leading to brain pathology. Thus, a possibility exists that restoring the balance of amino acids in the CNS following CHI using therapeutic measures may benefit the victims in improving their quality of life. In this investigation, we used a multimodal drug Cerebrolysin (Ever NeuroPharma, Austria) that is a well-balanced composition of several neurotrophic factors and active peptide fragments in exploring its effects on CHI induced alterations in key excitatory (Glutamate, Aspartate) and inhibitory (GABA, Glycine) amino acids in the CNS in relation brain pathology in dose and time-dependent manner. CHI was produced in anesthetized rats by dropping a weight of 114.6g over the right exposed parietal skull from a distance of 20cm height (0.224N impact) and blood-brain barrier (BBB), brain edema, neuronal injuries and behavioral dysfunctions were measured 8, 24, 48 and 72h after injury. Cerebrolysin (CBL) was administered (2.5, 5 or 10mL/kg, i.v.) after 4-72h following injury. Our observations show that repeated CBL induced a dose-dependent neuroprotection in CHI (5-10mL/kg) and also improved behavioral functions. Interestingly when CBL is delivered through TiO2 nanowires superior neuroprotective effects were observed in CHI even at a lower doses (2.5-5mL/kg). These observations are the first to demonstrate that CBL is effectively capable to attenuate CHI induced brain pathology and behavioral disturbances in a dose dependent manner, not reported earlier.

In inflammatory bowel disease (IBD), experimental models have proven to be important tools for evaluating potential therapeutic agents and for investigating the mechanisms of pathogenesis. Oxidative stress and the immune response have been associated with acetic acid (AA)-induced ulcerative colitis (UC). Our study aimed to evaluate, for the first time, the ability of a spore-based probiotic and an amino acid and immunoglobulin supplement in reducing tissue damage and inflammatory responses in an experimental animal model of UC. Forty-two Wistar rats were divided into six groups, receiving 1% carboxymethylcellulose, 4% AA, MegaSporeBiotic&trade, (MSB, 1 &times, 109 colony forming units/day) and MegaMucosa&trade, (MM, 70 mg/100 g/day). Pretreatment with MSB or MM alone and in combination significantly lowered inflammation and reduced damage to the colonic mucosa. Pretreatment with these agents resulted in levels of proinflammatory cytokines, vascular tight junction proteins, and measures of oxidative stress similar to those reported for methylprednisolone, one of the first-line therapies for moderate to severe activity of UC. The protection was further confirmed by histologic analysis of the colon tissue. In conclusion, pretreatment with probiotic spore-forming Bacillus strains and a supplement of amino acids in combination with immunoglobulins exhibited anti-inflammatory and antioxidant effects in an AA-induced rat model of UC.

Natural products black cumin&mdash, Nigella sativa (N. sativa) and wild garlic&mdash, Allium ursinum (AU) are known for their potential role in reducing cardiovascular risk factors, including antracycline chemotherapy. Therefore, this study investigates the effect of N. sativa and AU water and methanolic extracts in a cellular model of doxorubicin (doxo)-induced cardiotoxicity. The extracts were characterized using Ultraviolet-visible (UV-VIS) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, Liquid Chromatography coupled with Mass Spectrometry (LC-MS) and Gas Chromatography coupled with Mass Spectrometry (GC-MS) techniques. Antioxidant activity was evaluated on H9c2 cells. Cytosolic and mitochondrial reactive oxygen species (ROS) release was evaluated using 2&prime, 7&prime, dichlorofluorescin-diacetate (DHCF-DA) and mitochondria-targeted superoxide indicator (MitoSOX red), respectively. Mitochondrial membrane depolarization was evaluated by flow cytometry. LC-MS analysis identified 12 and 10 phenolic compounds in NSS and AU extracts, respectively, with flavonols as predominant compounds. FT-IR analysis identified the presence of carbohydrates, amino acids and lipids in both plants. GC-MS identified the sulfur compounds in the AU water extract. N. sativa seeds (NSS) methanolic extract had the highest antioxidant activity reducing both intracellular and mitochondrial ROS release. All extracts (excepting AU methanolic extract) preserved H9c2 cells viability. None of the investigated plants affected the mitochondrial membrane depolarization. N. sativa and AU are important sources of bioactive compounds with increased antioxidant activities, requiring different extraction solvents to obtain the pharmacological effects.

Nigella sativa (NS) has been used for centuries in various inflammatory conditions because of its anti-inflammatory and antioxidant activities. The study aimed to evaluate the anti-inflammatory, antinociceptive and antioxidant activity of Nigella sativa oil (NSO) in two models of acute (carrageenan-induced) and sub-acute inflammation (complete Freund&rsquo, s adjuvant induced) in rats. Materials and Methods: NSO was administered orally 1, 2 and 4 mL/kg in the acute phase. For subacute phase, NSO was administered 4 mL/kg, 7 days before or after inflammation induction, or in association with diclofenac 5 mg/kg. Results: The gas chromatography coupled with mass spectroscopy (GC-MS) analysis showed that NSO is an important source of bioactive compounds, especially p-cymene and thymoquinone. In the acute phase, 1.5 h after administration, NSO (2 and 4 mL/kg) determined an anti-inflammatory effect comparable with that of diclofenac. In the sub-acute administration, NSO had no anti-inflammatory effect. The analgesic effect of NSO was observed only in the sub-acute inflammation in the analgesy-meter test. NSO as treatment proved its antioxidant effect through the reduction of malondialdehyde (MDA) and oxidized glutathione (GSSG), and increases in hydrogen donor capacity (DH) compared to the control group, but the effect was not as intense as that of diclofenac. Conclusion: The present study has proven inconstant anti-inflammatory, analgesic and antioxidative properties of NSO.

(1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB1 gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB1 rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 &plusmn, 9.04 years, 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs&ndash, treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB1 SNPs and the risk of bleeding (p &gt, 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (p &gt, 0.05) except for the TG haplotype which had a trend toward statistical significance (p = 0.092). Among the risk factors for bleeding, only age &gt, 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB1 variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.

(1) Aim: The aim of this study was to assess the preferences of oral anticoagulants (OA) in patients diagnosed with deep vein thrombosis (DVT) of lower limbs or non-valvular atrial fibrillation (AF) requiring anticoagulation for medium/long term. (2) Materials and methods: the study included consecutive patients admitted with a diagnosis of either acute DVT of lower limbs (without signs of pulmonary embolism) or non-valvular AF who required oral anticoagulation, in a time frame of 18 months from January 2017 until June 2018. The following data were recorded: demographic variables, comorbidities (ischemic heart disease, arterial hypertension, heart failure, stroke, peripheral artery disease, diabetes mellitus, obesity), type and dose of OA (acenocoumarol, dabigatran, apixaban, rivaroxaban), complications due to the use of OA. (3) Results: AF patients were older and had considerably more cardiovascular comorbidities than DVT patients. Vitamin K antagonists (VKA) were more likely to be administered in patients with AF, as they had indication for indefinite anticoagulation. VKA were more frequently prescribed in patients with ischemic heart disease, heart failure, and diabetes compared with DVT patients. Moreover, complications related to OA use were more frequent in the VKA group. Almost half of patients with acute DVT (48.5%) were treated with direct OA (DOAC) rather than VKA, and only a quarter of AF patients (24.8%) were treated with DOACs.

(1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB1 gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB1 rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs–treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB1 SNPs and the risk of bleeding (p > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (p > 0.05) except for the TG haplotype which had a trend toward statistical significance (p = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB1 variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.

Introduction: Atherosclerosis represents the process by which fibrous plaques are formed in the arterial wall, increasing its rigidity with a subsequent decrease in blood flow which can lead to several cardiovascular events. Seeing as vitamin K antagonists are involved in the pathogenesis of atherosclerosis, we decided to investigate whether polymorphisms in genes that influence vitamin K metabolism might have an impact in modulating the risk of plaque formation. Patients and Methods: In the current study we included adult patients admitted in the Clinical Municipal Hospital of Cluj-Napoca without any carotid or femoral plaques clinically visible at the initial investigation, and a five year follow-up was subsequently performed. We recorded the following patient characteristics: age at inclusion, gender, area of living, smoking, presence of carotid and/or femoral plaques at five years, ischemic heart disease, arterial hypertension, atrial fibrillation, heart failure, diabetes mellitus, obesity, dyslipidemia, drug (oral anticoagulants, antihypertensives, hypolipidemic, anti-diabetic) use and status for the following gene polymorphisms: VKORC1 1639 G&gt, A, CYP4F2 1347 G&gt, T and GGCX 12970 C&gt, G. Results: We observed that the major predictor of both carotid and femoral plaque formation is represented by ischemic cardiac disease. VKORC1 and CYP4F2 polymorphisms did not predict plaque formation, except for VKORC1 homozygous mutants. Nonetheless, both VKORC1 and CYP4F2 interacted with ischemic cardiac disease, increasing the risk of developing a carotid plaque, while only CYP4F2, but not VKORC1, interacted with ischemic cardiac disease to increase the risk of femoral plaque formation. Conclusions: We documented that CYP4F2 and VKORC1 polymorphisms boost the proinflammatory plaque environment (observed indirectly through the presence of ischemic heart disease), increasing the risk of plaque development.

Cardio-oncology is a discipline based on early screening, monitoring, and treating chemotherapy-induced cardiotoxicity. There are many chemotherapeutics known for their cardiac toxic effects, including fluoropyrimidines. Fluoropyrimidine represents the cornerstone of many types of cancer and each year almost two million cancer patients undergo this treatment. Fluoropyrimidine-induced cardiotoxicity can be manifested in several forms, from angina pectoris to sudden death. This paper is a review of how the cardiotoxicity of fluoropyrimidines is presented, the mechanisms of its occurrence, its diagnosis, and management.

Background: Atrial fibrillation is a major health problem due to the stroke risk associated with it. To reduce stroke risk, oral anticoagulants (OAC) are prescribed using the CHA2DS2-VASc (Congestive heart failure, Hypertension, Age &ge, 75 years, Diabetes Mellitus, Stroke, Vascular disease, Age 65&ndash, 74 years, Sex category) risk score, a clinical probability assessment that includes a combination of risk factors predicting the probability of a stroke. Not all patients with high risk are receiving this treatment. The aim of this study was to assess physician adherence to clinical guidelines concerning the OAC treatment and to identify the factors that were associated with the decision to prescribe it. Methods: Registry data from 784 patients with non-valvular atrial fibrillation were evaluated in this retrospective cross-sectional study. Demographic data, subtype of AF, comorbidities associated with higher stroke and bleeding risk, and antithrombotic treatment received were recorded. We compared stroke and bleeding risk in patients with and without OAC treatment to determine if the clinicians followed guidelines: prescribed when necessary and abstained when not needed. Results: OAC treatment was administered in 617 (78.7%) patients. Of the 167 patients who did not receive OAC, 161 (96.4%) were undertreated according to their risk score, as opposed to those who received OAC in which the percentage of overtreated was 3.2%. Most undertreated patients (60.5%, p &lt, 0.001) were with paroxysmal atrial fibrillation subtype. Conclusions: The decision to use anticoagulants for stroke prevention was based on the type of atrial fibrillation, rather than on the risk of stroke as quantified by CHA2DS2-VASc as per the recommended guidelines.

Fluoropyrimidines, after more than 50 years of their discovery, are still the treatment of many types of cancer, and annually is estimated that two million patients use fluoropyrimidine treatment. The toxicity associated with fluoropyrimidines affects 30-40% of patients and some adverse effects can be lethal. Dihydroypyrimidine dehydrogenase is the main enzyme in the catabolism of 5-FU and DPD activity deficiency can cause important toxicity. There is an important reason for determinate DPD activity in order to improve patient safety and to limit potential life-threating toxicity. Now, are available multiple phenotypic and genotypic methods to determinate DPD activity, some of this methods have proven their usefulness in practice, but yet there are not routinely recommended in clinical practice. This review is another statement of the importance of determination DPD status, the phenotypic and genotypic methods that are available and can be used.

Acetaminophen (APAP) is one of the most used analgesics and antipyretic agents in the world. Intoxication with APAP is the main cause of acute liver toxicity in both the US and Europe. Spore-forming probiotic bacteria have the ability to resist harsh gastric and intestinal conditions. The aim of this study was to investigate the possible protective effect of Bacillus (B) species (sp) spores (B. licheniformis, B. indicus, B. subtilis, B. clausii, B. coagulans) against hepatotoxicity induced by APAP in rats. A total of 35 rats were randomly divided into seven groups: group I served as control, group II received silymarin, group III received MegaSporeBioticTM (MSB), group IV received APAP and served as the model of hepatotoxicity, group V received APAP and silymarin, group VI received APAP and MSB, group VII received APAP, silymarin and MSB. The livers for histopathological examination and blood samples were collected on the last day of the experiment. We determined aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (TAC) levels and zonula occludens (ZO-1), tumor necrosis factor &alpha, (TNF-&alpha, ) and interleukin 1&beta, (IL-1&beta, ) expression. APAP overdose increased AST and ALT. It slowly decreased TAC compared to the control group, but pretreatment with silymarin and MSB increased TAC levels. Elevated plasma concentrations were identified for ZO-1 in groups treated with APAP overdose compared with those without APAP or receiving APAP in combination with silymarin, MSB or both. The changes were positively correlated with the levels of other proinflammatory cytokines (TNF-&alpha, IL-1&beta, ). In addition, histopathological hepatic injury was improved by preadministration of MSB or silymarin versus the disease model group. Bacillus sp spores had a protective effect on acute hepatic injury induced by APAP. Pretreatment with MSB resulted in a significant reduction in serum AST, ALT, TNF-&alpha, ZO-1, TAC and also hepatocyte necrosis, similar to the well-known hepatoprotective agent&mdash, silymarin.