The third issue of IJBM has been published. Greetings to our authors! Thank you for your collaboration, either as readers, reviewers or donors. Today, we are at a time when an integration of all fields in the biomedical sciences has become vital in understanding the mechanisms of diseases. Therefore, our journal provides readers with a much broader scope of research. Nine original articles, on both basic and clinical research included in this IJBM issue, should provide our readers with a variety of scientific information, ranging from the study of disease mechanisms, to developing new diagnostic approaches and ultimately finding new drugs. These articles are drawn from several different countries. Living in one world, when the bright computer screen offers us endless possibilities, it is our hope that this journal will be a small focal point, where researchers will share their scientific achievements and wisdom with us. Any comments or suggestions on how this journal could be improved and heighten its usefulness are very welcome.
The first article, by Dr. Mrochek et al., addresses the differential diagnostics of atrial fibrillation and flutter. Atrial fibrillation/flutter (A-Fib/A-Flutter) are the most commonly encountered arrhythmias in clinical practice and continue to receive considerable research interest. A-Fib has many clinical symptoms quite similar to A-Flutter; however, they are quite different in terms of mechanism and management. Some patients have both A-Fib and A-Flutter and both arrhythmias are associated with the risk of thrombus formation and thromboembolism. Although the standard 12-lead electrocardiogram (ECG) is recorded in virtually every A-Fib and A-Flutter patient, it has only been recently, that information carried by the f-waves has been explored in some detail. A-Fib/A-Flutter analysis in non-invasive ECG recordings has received considerable attention in recent years, spurring the development of signal processing techniques for more advanced characterization of the atrial waveforms than previously available. This paper presents the results of the study of the method employed for differential diagnostics of Fbr/Flt, based on the spectral analysis of the atrial electrical activity, and how to conduct its clinical trials. The authors had developed this method based on blind source separation, which offers a high reliability to extract atrial ECG based on the surface 12-lead ECG. Also, the frequency of ectopic activity can be estimated based on this spectrum. The offered algorithm is easy to use in choosing an alternative between a pharmacological and surgical correction of patients with A-Fib and A-Flutter. Two other articles are addressed on obesity and the metabolic syndrome. Young scientists from CIS and India have devoted their research to studying this problem. Metabolic syndrome, described as the ‘silent killer’, has become a serious global problem. Prolific studies suggest that patients with metabolic syndrome possess a greater risk of developing significant clinical consequences, the two most prominent and dreaded of which are, diabetes mellitus and coronary heart disease. The increasing prevalence of MS occurs with the obesity epidemic. Almost two-thirds of United States’ population is overweight or obese, while more than one-fourth of the population meets the diagnostic criteria for the syndrome, also considered an emerging epidemic in European and Asian countries. Metabolic syndrome is a cluster of abnormalities with the basic characteristics being insulin resistance and visceral obesity. An unbalanced and arrhythmic autonomic nervous system is a major cause of the metabolic syndrome. Dr. Kiran Thorat and Dr. Sandip Ghuge investigated the relationship between obesity and cardiovascular autonomic functions. They studied the relationship between body mass index and cardiovascular sympathetic and parasympathetic functions. Increased sympathetic activity and to some degree decreased parasympathetic activity were found to be correlated with obesity. Recently, this characteristic of the unbalanced autonomic function has been the focus of active investigation. Unbalanced autonomic function is very multiplex. An abnormal parasympathetic predominance is observed in the abdominal territory (abdominal fat), and abnormal sympathetic predominance in the thoraco-muscular territory (increase in insulin resistance and blood pressure). Dr. Nigora Z. Srojidinova, studied the relationship between impaired glucose tolerance and hyperinsulinemia with target organ damage in hypertensive patients. The author observed that hyperinsulinemia accentuated an increase in left ventricular (LV) hypertrophy, endothelial dysfunction and microalbuminuria. This is clinically relevant since these markers of target organ damage are associated with an increased risk of fatal and nonfatal cardiovascular events. Dr. Kurbanov and colleagues examined the prevalence, clinical hemodynamic characteristics and long-term prognosis of patients with the familial form of dilated cardiomyopathy (DCM). Familial DCM is a not such a rare disease as it was earlier believed. Family-based studies of first-degree relatives during the past few decades have established that familial DCM can be identified in 20% to over 50% of patients diagnosed with idiopathic dilated cardiomyopathy. Authors examined 221 patients with DCM, of which 27 cases (12.2%) were identified as having familial cardiomyopathy. They presented a very interesting pedigree with familial DCM in 3 brothers. Most familial DCM is transmitted in an autosomal dominant inheritance pattern, although all inheritance patterns have been identified (autosomal recessive, X-linked, and mitochondrial). Till recently, familial DCM genetic studies have identified mutations in over 30 genes. The high frequency of familial DCM indicates the importance of including a three- to four-generation family history and clinical screening of first-degree family members, if new idiopathic DCM cases are detected. Data received in study by Kurbanov et al., showed that the familial form and age below 30 years are associated with a rapid progression of the clinical course, coupled with increasing mortality in the first 12 months of followup. The rapid progression of familial DCM should be considered when scheduling heart transplantation as the treatment of choice. The following article, by Dr. K. Vitlianova, addresses the issue of clinical determinants of plasma metalloproteinase-9 (MMP-9) in systolic chronic heart failure. Heart failure is a worldwide problem. According to the American Heart Association, heart failure affects nearly 5.7 million Americans of all ages. With improvement in survival of acute MIs and a population that continues to age, heart failure will continue to increase in prominence, as a major health problem. The matrix metalloproteinases (MMPs) are being increasingly recognized as key players in the remodeling of the left ventricular myocardium that accompanies the progression to heart failure. MMPs regulate the matrix turnover, which is a highly dynamic structure, responsive to biological and mechanical stimuli and subject to continuous reconstruction. MMPs constitute a family of enzymes with over 20 different species. Elevated MMP-9 plasma levels are associated with increased LV diastolic dimensions and increased wall thickness in humans. Thus, as expected, in the present study, authors found that MMP-9 was independently correlated with the degree of cardiac dysfunction and clinical parameters depending on it, including systolic blood pressure, atrial fibrillation, as well as the presence of chronic obstructive pulmonary diseases. Further studies are warranted on the concrete mechanisms of MMP-9 variations in patients with chronic heart failure. The MMPs have also been scrutinized in a paper submitted by Dr. Govorova et al. The authors devoted their research to the genetic analysis of the matrix metalloproteinase’s gene polymorphisms in patients with hereditary connective tissue diseases (HCTD). Heritable disorders involving the connective tissue are among the most common genetic diseases in humans. HCTD are a heterogeneous group of generalized single-gene-determined disorders that affect one or another of the primary elements of the connective tissues (collagen, elastin, or ground substance), and they may seriously interfere with the normal skeletal and joint growth and development. The rapidly growing knowledge of the molecular biology of the extracellular matrix has changed many preexisting concepts for the pathogenesis of heritable connective tissue diseases. The spectrum of genetic matrix disorders is much broader than previously believed and now also includes diseases of the organs such as the kidney, eye and muscles. A wide variety of diseases has been associated with the collagens, caused by mutations in at least 27 different collagen-associated genes. Dr. Govorova et al., analyzed the frequency of polymorphisms in the genes MMP1 (1607insG), MMP9 (C-1562T), MMP12 (A-82G), TIMP1 (S536T) to identify alleles and genotypes associated with HDCT. The carrier state of the mutant allele T of the gene MMP9 and the mutant allele G of the gene MMP1 were found to be associated with an increased risk of producing signs of HDCT. Further studies are required to test these associations.The following article has been devoted to the development of new antiviral substances. Dr. Olena Bogorad-Kobelska et al., examined the toxicity, antiviral and interferon-inducing activities of diphenyl derivatives versus tilorone for different cell cultures. From among the low-molecular synthetic inducers of interferon tilorone, dihydrochloride was found to be the most effective. In 1970, Krueger and Mayer reported that tilorone hydrochloride (bis-diethylamino ethyl-fluorenone) induced antiviral activity in mice after oral administration. This antiviral activity was shown to be associated with induction of interferon. Tilorone is the first recognized synthetic, low-molecular-weight compound that is an orally active interferon inducer, and is also reported to have anti-neoplastic and anti-inflammatory actions. However, there are some restrictions regarding tilorone use, which is why the search for tilorone derivatives or analogues with lower toxicity and higher efficiency is an urgent need and is being researched in a number of laboratories across the world. The authors have noted that the structural analogues of tilorone - diphenyls - have been identified to show a high degree of biological activity; they are less toxic than tilorone and may be hailed as the new IFN inducers and also as compounds with the potential of great promise in producing new antiviral drugs. In the following article, Dr. Bekmetova et al., studied the efficacy of Ivabradine and Bisoprolol based on the results of flow-mediated dilation in patients with coronary heart disease. They estimated the reactions of the different applications of Ivabradine and Bisoprolol in patients with stable angina, based on initial clinical and hemodynamic parameters, exercise tolerance and flow-mediated dilation. Treatment with Ivabradine significantly increased the chronotropic effect in the exercise test, improving the endothelial function, as assessed by the results of the flow-mediated dilatation test. Several studies have demonstrated that patient outcomes improve when guideline recommendations, based on the rigorous assessment of evidence-based research, are applied in clinical practice. European and ACC/AHA Guidelines for the Management of Patients with Chronic Stable Angina noted that it was beneficial to start and continue beta-blocker therapy indefinitely in all patients who have had a myocardial infarction, acute coronary syndrome or left ventricular dysfunction, with or without heart failure symptoms, unless contraindicated. According European Guidelines sinus node inhibitors, such as ivabradine, with negative chronotropic effects both at rest and during exercise, have proven anti-anginal efficacy and may be used as an alternative agent in patients who do not tolerate beta-blockade. The Guidelines, based on all the relevant evidence, helps physicians to select the best possible management strategies for the individual patient, suffering from a specific condition, not only considering the impact on outcome, but also the risk-benefit ratio of a particular diagnostic or therapeutic procedure.The final paper by Dr. Karnitsky is devoted to modern non-drug treatment. This study discusses the advantages of the various types of non-drug treatment, including the possibilities of their application in the most common diseases. As debate continues to identify the ideal medicine, the above interventions will definitely play a definitive role in future treatment options.