Functional dynamics of myocardial injury biomarkers production during acute isoprenaline treatment in rats

Introduction: Isoprenaline or isoproterenol (1-(3,4-dihydroxyphenyl)-2-isopropylaminoethanolhydrochloride; ISO), a synthetic b-adrenergic agonist, can be used to establish myocardial ischemia, cardiotoxicity, necrosis and/or an experimental model of infarction in rats. Aim: Determination of the dynamics of myocardial injury biomarkers production of aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and high-sensitive troponin T (hsTnT), with changes on electrocardiogram (ECG) parameters during the subcutaneous aplication of ISO in male Wistar rats. Material and methods: All animals (n = 23) were divided into two groups: control group (n = 11) treated with a saline solution, during two consecutive days (0,2 ml/kg b.m. daily, sc); and the ISO group (n = 12) treated with isoprenaline, during two consecutive days (85 mg/kg b.m. daily, sc). Blood was drawn from the rat tail vein in both groups, in order to determine serum activity levels of myocardial injury biomarkers, and an ECG (n = 6) was registered prior to the application, as well as 48h following the first dose of of saline solution or isoprenaline. Results: In comparison to the control group, in which no significant enzyme activities elevation (p > 0.05) nor ECG changes were registered, ISO group presented a significant rise of two clinically significant biomarkers of acute myocardial injury/myocardial infarction (AMI), CK (p = 0.05) and hsTnT (p < 0.01), as well as an ST segment elevation, with a patognomonic ECG change. Conclusion: Obtained results support previous studies, proving that isoprenaline represents an adequate experimental model for myocardial injury/AMI induction, and a "golden standard" for evaluating potential cardioprotective effects of pharmacological and non-pharmacological therapeutic modalities, with the ultimate goal of lowering the degree of lesions and improving post-infarction myocardium function.

Mental health and COVID-19 pandemic: The literature review

Mental health (MH) and illness reflect bio-psycho-social balance/imbalance and extend into multidimensional space. In the current pandemic, the entire area of MH/illness is at increased risk of contamination not only by infection, but also by numerous other aspects of this complex public health crisis. There are at least three mechanisms by which the COVID-19 pandemic can create new-onset mental conditions: 1) Psychological factor - increased degree of emotional suffering after extremely severe traumatic events or long-term life-threatening exposures; 2) Social factor - risks related to interaction with the environment: a) emotional deprivation; b) cognitive disintegration related to infodemia and c) existential, primarily economic fears that destabilize relationships (within the family and beyond); and 3) Biological factor - neuropsychiatric effects of the virus itself. In addition to the new-onset conditions, the pandemic also has an impact on people who already have a history of mental disorders. This review paper will present the most important information from relevant sources related to mental health and the COVID-19 pandemic related to the first year of exposure. Emphasis will be on research that has attracted attention with sample size and representativeness, as well as a reliable methodology, with the aim of not losing sight of the heterogeneity of the pandemic effects on mental health.

Significance of thiol-disulfide balance in SARS-CoV-2 infection

Studies of the molecular mechanisms regarding interaction of different viruses with receptors on the host cell surface have shown that the viral entry depends on the specific relationship between free thiol (SH) groups and disulfides on the virus surface, as well as the thiol disulfide balance on the host cell surface. The presence of oxidizing compounds or alkylating agents, which disturb the thiol-disulfide balance on the surface of the virus, can also affect its infectious potential. Disturbed thiol-disulfide balance may also influence protein-protein interactions between SARS-CoV-2 protein S and ACE2 receptors of the host cell. This review presents the basic mechanisms of maintaining intracellular and extracellular thiol disulfide balance and previous experimental and clinical evidence in favor of impaired balance in SARS-CoV-2 infection. Besides, the results of the clinical application or experimental analysis of compounds that induce changes in the thiol disulfide balance towards reduction of disulfide bridges in proteins of interest in COVID-19 infection are presented.

Patients characteristics and prognostic implications of type 2 diabetes mellitus in heart failure with preserved, mid-rang reduced and reduced ejection fraction

Introduction: Type 2 diabetes mellitus (T2DM) is frequent in patients with heart failure (HF) and correlated with an increased morbidity and mortality. The features and outcomes of patients with and without T2DM, depending on the HF type (HF with preserved: HFpEF, mid-range: HFmrEF; and reduced ejection fraction: HFrEF), are inefficiently explored. Aim: To explore the impact of T2DM on clinical features and one-year overall mortality in patients with HFrEF, HFmrEF and HFpEF. Material and methods: A prospective, observational study was conducted, including patients with HF at the Department of Cardiology, Clinical Center of Serbia, Belgrade. The enrolment occurred between November 2018 and January 2019. The study outcome was one-year all-cause mortality. Results: Study included 242 patients (mean-age, 71 ± 13 years, men 57%). T2DM was present in 31% of patients. The proportion of T2DM was similar amid patients with HFrEF, HFmrEF, and HFpEF. Regardless of the HF type, patients with T2DM were probably older and had a higher prevalence of myocardial infarction, other types of coronary disorder or peripheral arterial disorder (all p < 0.001). Also, chronic kidney disease was more prevalent in T2DM (p < 0.001). In HFpEF, T2DM patients were commonly female, and usually had hypertension and atrial fibrillation (all p < 0.001). Estimated one-year total mortality rates were significantly higher in T2DM patients. It also emerged as a unique predictor of higher mortality in HFrEF (HR; 1.33; 95% CI; 1.34 - 2.00), HFmrEF (HR; 1.13; 95% CI; 1.0 - 1.24) and HFpEF (HR; 1.21; 95% CI; 1.09 - 1.56), all p < 0.05. Conclusion: Compared with non-diabetics, patients with HF and T2DM are older, with higher prevalence of comorbidities and greater one-year mortality, regardless of HF type. Heart failure is a unique predictor of mortality in all HF types in multivariate analysis. Considering the increased risk, T2DM requires meticulous screening/diagnosis and contemporary treatment to improve outcomes.

The role of plant polyphenols in the health preservation: Effects on human cardiometabolic function

Regardless of the continuous improvement of diagnostic possibilities and the organizational structure of the healthcare system that contribute to the reduction of the complicated courses of diseases, modern socio-economic and environmental stressors, life habits and increased fluctuation in the psychological functioning of an individual still have a great influence on the overall burden of human diseases. At present, etiological factors and pathogenic mechanisms of numerous diseases are known, thus enabling their continuous and timely pharmacotherapy. However, for progressive diseases or those associated with numeorus complications, pharmacological treatment can lead to the side effects, and preventive measures are highlighted as the main strategy in the management of such diseases, especially in chronic non-communicable diseases such as cardiovascular diseases (CVDs). One of the preventive measures is timely and qualitative supplementation of the diet with beneficial micronutrients and oligoelements. Their main sources are represented in plant fibers that synthesize biologically active substances with a polyphenolic ring in their structure, called natural polyphenolic compounds (NPC). Decades of NPC research have brought new insights into the potential modification of existing pharmacotherapy of numeorus diseases. Currently, it is known that many polyphenols have an optimal pharmacological profile with cardioprotection and at the center of their overall effects. Research into the mechanisms of polyphenolic action is exhaustive, their interactions with numerous subcellular structures have been described, and they are refered as promising molecules, with the potential to modify key pathogenetic elements that lead to the progression of various diseases. So far, their numerous effects on endothelium, smooth muscle cells and lipid cells involved in the process of atherogenesis are known, their antidiabetic, antioxidant, anti-inflammatory and immunomodulatory properties have been proven, and the synergy with the intestinal microbial populations has recently been known to contribute to their beneficial effects. This paper has the aim to point out the most important mechanisms that NPC use to improve general functionality of the organism by stimulating its defense capacity, prolonging cell life and delaying its overall aging. As the most important cardioprotective nutrients, a special focus is given to their beneficial effects on cardiovascular and metabolic function.

SARS-CoV-2 immunity and an overview of the COVID-19 vaccines

The remarkable development of a large number of vaccines against COVID-19 in a very short period of time represents one of the greatest successes of medicine and science in history, and mass vaccination at the global level will be crucial for prevention and mitigation of COVID-19. However, there are still numerous open questions about the vaccines, and the protection they provide, and answers to those questions will not only help to control this pandemic, but they will also prepare us to react better in case of future outbreaks. This review will present the latest findings on the immune response to SARS-CoV-2 and give an update on COVID-19 immunity. It will also provide an overview of the most important vaccines against COVID-19, especially those available in Serbia, with an emphasis on their immunogenicity, efficacy and safety, as well as the platforms used for their development. In addition, a special attention will be given to open issues related to immunization against COVID-19, such as the duration of post-vaccination immunity, the degree of protection against new virus variants and the need for booster doses and mixing and matching of different COVID-19 vaccines.

Epidemiology of COVID-19: What have we learnt until now?

The first case in the outbreak of atypical pneumonia of unknown etiology, later confirmed as disease caused by SARS-CoV-2, was described in Wuhan (China) on December 8, 2019. The rapid expansion of COVID-19 cases prompted the World Health Organization (WHO) to declare a global health emergency, and on March 11, 2020, COVID-19 was officially classified as a pandemic disease by the WHO. It is generally accepted that both genders and all ages in the population are susceptible to SARS-CoV-2 infection. Data from the real life also show difficulties in reaching the threshold of herd immunity. Thanks to the vaccination, some populations are approaching the theoretical threshold of immunity, but the spread of the virus is still difficult to stop. If we add to that the fact that we still do not know how long immunity lasts after the infection, the conclusion is that vaccination is unlikely to completely stop the spread of the virus, and that we must think about it. Vaccines certainly significantly reduce the hospitalization rate and mortality rate, and the assumption is that the virus will not disappear soon, but the severity of the disease and its fatality will be of marginal importance. The development of the epidemiological situation related to the COVID-19 is constantly changing and it significantly differs in various parts of the world, which is affected by differences in financial resources, health infrastructure and awareness of prevention and control of the COVID-19. Attempts are being made to make dynamically adjusted strategies in response to the COVID-19 pandemic, that is, the new normality.

Factors associated with seasonal influenza immunization in people with chronic diseases

Annually, at a global level, 3 to 5 million people present severe clinical forms of seasonal influenza and up to 650 000 people die of influenza-related complications. People with chronic diseases, such as cardiovascular, pulmonary, renal, hepatic, neurologic, hematologic and metabolic diseases or those reciveing immunosuppressive therapy, constitute a high-risk population group for the development of influenza-related complications, more severe clinical course and poorer health-related outcomes. Due to all of the above, people with chronic diseases are of high priority to receive the influenza vaccine. Immunization represents the key strategy to prevent influenza both in terms of effectiveness and health care costs. Based on the World Health Organization (WHO) recommendations, adequate seasonal influenza immunization coverage among people with chronic diseases is set at 75%. However, few countries achieve this threshold. Understanding predictive factors of vaccination, at different levels of health care delivery (such as individuals, service providers, health policy), is essential to secure acceptance of influenza immunization and achieve the recommended level of vaccination coverage. In this mini review, all the available evidence regarding seasonal influenza vaccination coverage is summarized, alongside factors associated with vaccine uptake in people with chronic diseases as a whole, as well as according to specific diseases such as: cardiovascular and pulmonary disorders, diabetes and cancer. Based on the reviewed empirical evidence, a wide spectrum of factors associated with immunization against influneza was found in people who have chronic diseases. Although diverse, these factors can be systematized into 4 distinctive groups: socio-demographic characteristics, individual attitudes and beliefs, health promoting behaviors and factors related to the health care system. Further efforts are needed to improve the seasonal influenza vaccination coverage. The immunization strategy needs to include the health care system and the community to support people with chronic diseases to continously accept the influenza vaccine.

The influence of genetic polymorphisms on the toxicity of platinum-based chemotherapy in the treatment of non-small cell lung cancer

Lung cancer remains one of the most frequent and the deadliest of malignant diseases throughout the world. Target and immune therapy have revolutionalized the treatment of this disease, but platinum-based chemotherapy still has a place in the treatment algorithm. The toxicity profile of cisplatin is well known and can be a limiting factor in the adequate treatment delivery of the drug. There are important inter-individual differences in the efficacy and the toxicity of all chemotherapy drugs, which cannot be explained solely by the characteristics of the tumor. In order to define predictive factors for the occurrence of toxic effects, numerous genetic alterations have been investigated - especially single nucleotide polymorphisms (SNPs). The investigated genes are those involved in DNA repair mechanisms, signal pathways of apoptosis, DNA synthesis, transport mechanisms, but often with inconclusive and opposing results. It is clear that the effect of SNPs on the occurrence of cisplatin toxicity cannot be explained by investigating just one or several genes alone, but epigenetic interactions must be investigated, as well as interactions with outside factors. The study of SNPs is, however, a relatively simple and inexpensive method and, as such, can be used as one of the prognostic tools for everyday practice.

Treatment of critically ill COVID-19 patients: Practical guidelines

The coronavirus disease pandemic (2019) has burdened health systems around the world with a large number of severe patients in a short period of time. According to the law of large numbers, a significant number of critically ill COVID-19 patients appear in such conditions which require treatment in the intensive care unit. That percentage of those patients is around 3 - 5% in different countries. It is similar in Serbia; however, every rule has its exceptions. KBC "Dr Dragiša Mišović-Dedinje" in Belgrade has been determined to take care of the most difficult COVID-19 patients since the beginning of the epidemic due to its space, organizational and personnel possibilities. Out of the total number of patients treated in KBC "Dr Dragiša Mišović-Dedinje", about 25% of patients were treated in the intensive care unit for the above mentioned reasons. Guided by valid treatment protocols, Anesthesiology and Intensive Care clinic of the KBC "Dr Dragiša Mišović-Dedinje" has developed its own work protocols for rapid diagnosis, isolation and clinical management of such difficult patients. These protocols are important not only for the treatment of the most severe COVID-19 patients, but also for the best utilization of hospital resources, as well as for the prevention of the spread of the infection to the medical staff. Extensive experience in the treatment of critically ill patients was gained from the entire engagement during the epidemic, experienced doctors, anesthesiologists-intensivists with great knowledge in the field of work in the intensive care unit, but also managers of clinics and institutions, who can share their experience with health care policy makers. It is clear that in the future, the capacities and organization of work in the field of intensive care medicine should be redefined, as well as health workers should be trained to work in the most demanding field of medicine. Expert experience in the form of practical guidelines, derived from over fourteen months of continuous work in the red zone of COVID-19, where they fought for every breath of the patient, in this review are translated into simplified guidelines for orientation of those who find themselves in a similar situation.