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Vol. 43, 2007


bullet 4'2007


Prognostic significance of тhe cell cycle regulators p21, p27, p53, Rb and proapoptotic multidomain proteins Bax and Bak for the cancerogenesis: a critical opinion opinion   – 43, 2007, No 4, 5-11.
M. D. Apostolova and G. Tchernev
Institute of Molecular Biology, Bulgarian Academy of Sciences -- Sofia
Summary: The mechanisms of tumor cell survival are regulated by overcoming cell cycle check-points and immunological responses. These mechanisms are also part of uncontrolled local tumor growth and metastasis. The disturbances of cell proliferation, differentiation and apoptosis are based on specific and incompletely characterized signal-transduction pathways within the tumor cells and between them and the immune system. Detailed investigations and characterizations of the mechanisms involved are required to describe better the tumor behavior, to prepare more reliable prognosis and to suggest new therapeutic strategies.
Кеy words: Apoptosis, cell cycle, autoimmunity, Bax, NKC, KIR
Address for correspondence:
Georgi Tchernev, M. D., Department of Dermatology, Venereology, Allergology and Pneumology, Ostseeclinic Kuehlungsborn, Waldstrasse 51, 18225 Kuehlungsborn, Germany, tel. +49 1622643815 (GSM), e-mail: georgi_tchernev@yahoo.de




Adoptive immunotherapy for cancer – 43, 2007, No 4,  12-16.
G. Milchev
IMB – Bulgarian Academy of Sciences -- Sofia
Summary: Tumor-induced suppression and immune-based regulatory factors limit the effectiveness of vaccine-induced, tumor-specific T cells. Induction of lymphopenia can lead to eliminating inhibitory immune cells in the host such as T-regs and to increased production and availability of immune response-stimulating cytokines such as IL-7 and IL-15, resulting in enhanced CD8+ T cell activity. Preclinical studies have shown that the induction of lymphopenia by chemotherapy or radiation can enhance the antitumor efficacy of several distinct, cell-based immunotherapeutic approaches. It is postulated that vaccination during homeo­stasis-driven proliferation may serve to educate the developing T cell repertoire and lead to enhanced T cell memory against tumor-associated self antigens. The influence of hematopoietic stem and progenitor cell transfer on the in vivo function of adoptively transferred CD8+ T cells is evaluated.
Key words: adoptive transfer, tumor infiltrating lymphocytes, regulatory T cells, stem and proge­nitor cells, antigen-presenting dendritic cells
Address for correspondence: Georgi Milchev, M. D., 54 Skobelev Blvd., Bg -- 1606 Sofia, tel. 359 2 953-0983, e-mail: gmilchev@bio21.bas.bg




Oxidative stress, diabetes mellitus and embrio-foetal malformations malformations    – 43, 2007, No 4, 17-21.
K. Todorova-Ananieva
SHATOG “Maychin dom” -- Sofia
Summary: Maternal diabetes is associated with high incidence of embrio-foetal complications -- spontaneous abortion and congenital malformations, genesis of which involves except hyperglycemia additional mechanisms -- oxidative stress, apoptosis etc. They exert complex influence on the embryo in the very early stage of preimplantation blastocyst, and are cause for diabetic insult. Many studies of pregnant women confirm the thesis, that diabetic embryonic dysmorphogenesis is multifactorial. It is defined by the individual embryonic sensitivity towards teratogens. Nowadays, the hypothesis of the role of oxidative stress in genesis of diabetic embryo-fetal complications is supported more and more.
Key words: diabetic embryopathy, oxidative stress, antioxidant protection, individual teratogen susceptibility
Аddress for correspondence: Katya Todorova-Ananieva, M. D., SHATOG “Maychin dom”, 2, Zdrave Str., Bg --1432 Sofia, GSM +359 888408203, e-mail: todorova_kate@yahoo.com




Left ventricular hypertrophy in the light of ambulatory blood pressure – 43, 2007, No 4, 22-30.
D. Raev
Cardiology Clinic and ICU, Medical Institute -- Ministry of Interior -- Sofia
Summary: The widely used ambulatory blood pressure (BP) monitoring revealed a seriously discrepance between office BP and ambulatory BP (ABP). ABP gives us more information than office BP about left ventricular (LV) hypertrophy. ABP correlates closer than office BP with LV mass and especially with its appropriateness. Patients with morning hypertension, those with increased BP variability and nondippers have larger LV mass, independently of 24-hours BP. Patients with masked hypertension have similar chance with those with sustained hypertension to develope LV hypertrophy. Patients with isolated office hypertension have larger LV mass and they have LV hypertrophy more frequently than individuals with sustained normotony. The white coat effects is also associated with larger LV mass. Based on treatment induced ABP reduction, one can predict LV mass regression more correctely. The aim of this review was to consider significance of ABP for the assessment of LV mass changes in arterial hypertension.
Key words: left ventricular mass, ambulatory blood pressure, dipping status, morning hypertension, blood pressure variability, masked hypertension
Address for correspondence: Assoc. Prof. Dimitar Raev, M. D., Medical Institute -- Ministry of Interior, 79 Skobelev Str., Bg -- 1606 Sofia, e-mail: draevbg56@yahoo.com



Blood flow-mediated vasodilatation -- pathophysiologic basis and methodology of the study  – 43, 2007, No 4,  31-35.
I. Simova and S. Denchev

Clinic of Cardiology, University Hospital “Alexandrovska” -- Sofia
Summary: Early detection and primary prophylaxis of diseases has been receiving much attention in clinical practice. In the early stages of the atherosclerotic process, there is a functional impairment in endothelial cells with a pathologic vasoconstrictory response to stimuli normally causing vasodilatation. This can be detected by measuring the reactivity of the brachial artery to hyperemia after an ischemic stimulus -- flow-mediated vasodilatation. The pathophysiologic basis of the method, appropriate technique and requirements to the investigator are discussed.
Key words: atherosclerosis, endothelial changes, flow-mediated vasodilatation, technique
Address for correspondence: Iana Simova, M. D., Clinic of Cardiology, University Hospital “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg -- 1431 Sofia, e- mail: ianahr@yahoo.com




Immunologic aspects of the turnover of elastin in some connective tissue diseases  – 43, 2007, No 4,  36-43.
M. Bogdanova
Department of Biology and Pathophysiology, Medical University -- Pleven
Summary: Antibodies against alpha-elastin (elastin breakdown product) and tropoelastin (TE) (elastin precursor) are found in serum of all healthy persons and correlate with their respective serum peptide levels. The aim of this scientific survey was to present and analyse the immunologic aspects of the turnover of elastin in some connective tissue diseases according to different authors. Significantly elevated were serum levels of antibodies to alpha-elastin (AEAbs) from class IgG in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SS), polyarteritis nodosa, polymyalgia rheumatica. AEAbs from subclasses IgG1 and IgG3 were significantly elevated in patients with SS, as well as in those with systemic and subacute cutaneous lupus in comparison with these in healthy persons. Significantly elevated were IgA AEAbs in SS and in men with ankylosing spondylitis (AS), IgM AEAbs in women with AS aged 41-50 yrs., IgE AEAbs in patients with SS. This suggests increased elastin degradation in these patients. The serum levels of antibodies to TE from class IgG were significantly decreased in patients with SLE, SS, polymyositis, vasculitis, fibromyalgia syndrome, polymyalgia rheumatica in comparison with these in healthy persons. This suggests decreased elastin synthesis in them.
Key words: antibodies, elastin, connective tissue diseases
Address for correspondence: Marieta Bogdanova, M.D., Department of Biology and Pathophysiology, Medical University, 1, Sv. Kl. Ohridski Str., Bg -- 5800 Pleven, tel./fax: +359 64 801 603, e-mail: mbecht02@abv.bg





bullet 3'2007


Coronary syndrome X -- a vague diagnosis – 43, 2007, No 3, 5-14.   
S. Denchev
Clinic of Cardiology, MHAT “Alexandrovska” -- Sofia
Summary: The triad of chest pain, positive exercise electrocardiogram and angiographically normal or with minimal lesions coronary arteries has been known for years and is called coronary syndrome X (CSX). The patients with this syndrome have often debilitating symptomatology, requiring hospital readmissions, increased psychological morbidity and a poor quality of life. Of a greater importance are the recently published data, that the long term prognosis may be not as benign as previously believed. In the review, the possible pathophysiological mechanisms, including myocardial ischaemia, endothelial dysfunction, abnormal pain perception, hormonal and metabolic factors are discussed. It is noted that the treatment is not substantiated. It is concluded that the patients with CSX are a heterogeneous group with different pathogenetic mechanisms involved. It is necessary that the patients with increased risks toward future unfavorable cardiovascular events have to be defined in order to provide an adequate preventive treatment.
Key words: coronary syndrome X, pathophysiologic mechanisms, prognosis
Address for correspondence:
Assoc. Prof. Stefan Denchev, M. D., Clinic of Cardiology, MHAT “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg 1431 Sofia, e-mail: svdbg@yahoo.bg, svdbg@mail.bg


ACE inhibitors, AT1 blockers or the combination of both – 43, 2007, No 3, 15-21. 
G. Krasteva(1) and E. Lakova(2)
(1)Department of Physiology and Experimental and Clinical Pharmacology
(2)Department of Biology and Pathophysiology
Medical University -- Pleven
Summary: The Renin-Angiotensin System (RAS) blockade with ACE inhibitors and AT1-receptor blockers is one of the most successful therapeutic approaches in modern medicine. Along with the common therapeutic and preventive advantages such as blood pressure decrease, vasoprotection, renoprotection, cardioprotection, there are also a number of peculiarities in their reaction to certain biochemical components in and outside RAS -- bradykinin, hematological peptide, AT-(1-7), AT2-receptors, local RAS, PPAR, etc. They create a basis for finding the fine differences in their therapeutic application affecting both the better motivated choice between the two groups of medicines and the possible positive effects of combining them.
Key words: ACE inhibitors, AT1-blockers, combined RAS blockade
Address for correspondence:
Genka Krasteva, M.D., Department of Physiology and Experimental and Clinical Pharmacology, Medical University, 1 Kl. Ohridski Str., Bg  5800 Pleven, tel. +359 64 884 134, e-mail: krusteva_med@abv.bg


Staphylococcal superantigen and common skin diseases – 43, 2007, No 3, 22-25. 
M. Gencheva(1), Kr. Nikolov(1) and M. Baleva(2)
(1)Medical University -- Varna
(2)Medical University -- Sofia
Summary: During the last two decades, the morbidity from staphylococcal and streptococcal infection has been increased significantly. There are many reports concerning the main role of bacterial superantigens in the induction of inflammatory process in such disorders as psoriasis and atopic dermatitis. Staph. aureus and Streptococcus are the main pathogens, producing toxins -- “superanigens”. They mediate a massive inflammatory response that goes around the traditional immune pathways. This review discusses the basic immune mechanisms of the response to the staphylococcal superantigen in patients with atopic dermatitis and psoriasis.
Key words: Staphyloccocal superantigen, atopic dermatitis, psoriasis
Address for correspondence:
Prof. Marta Baleva, M. D. University Alexandrovska Hospital, 1, Sv. G. Sofiiski Str., Bg -- 1431 Sofia, PO Box 45, e-mail: marta_baleva@yahoo.com




bullet 2'2007

MS-like syndrome and other neurologic manifestations in rheumatic diseases  –  43, 2007, No 2,  5-13.
S. Monov
Clinic of Rheumatology, Medical Unuversity -- Sofia

Summary: Neuropsychiatric manifestations are frequently seen in rheumatic diseases. Aim of this study was to present the most often neurologic manifestations in some of these diseases, including those characteristic of multiple sclerosis (MS). Most often (between 25 and 79%) and diverse are the neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE). Better studied in SLE are the disorders of the humoral immunity -- a variety of antibodies. The presence of antiproteasome antibodies may be used as a marker for MS, and respectively for its differentiation from MS-like syndromes seen in some rheumatic diseases. Neuropsychiatric deviations are described in Sjogren’s syndrome (migraineous headache, motor disturbances, seizures, encephalopathies, aseptic meningitis etc.); in antiphospholipid syndrome (cerebrovascular incidents etc.); in Behcet’s syndrome (headache, paresthesias, diplopia, sensitivity disorders, cerebellar ataxia, hemiplegia, ophthalmoplegia etc.); in Wegener’s granulomatosis (peripheral neuropathy, multiple mononeuritis, neuropathy of craniocerebral nerves, ophthalmoplegia, epileptic seizures, cerebrovascular incidents etc.). MS-like syndrome is most often presented in patients with SLE
Key words: neuropsychiatric systemic lupus erythematosus, antiphospholipid syndrome, Sjogren’s syndrome, Behcet’s syndrome, Wegener’s granulomatosis, multiple sclerosis, MS-like syndromes
Аddress for correspondence: Simeon Monov, M.D., Clinic of Rheumatology, Medical University, 13, Urvich Str., Bg -- 1612 Sofia, tel. +359 2 958-29-27


 Anogenitally located HPV associated lesions –  43, 2007, No 2, 14-24.
G. Tchernev
Department of Dermatology and Immunology, Municipal Hospital Dessau, Academic Educational Hospital of the Martin Luther University -- Halle-Wittenberg, Germany

Summary: Visible papillomavirus-associated benign and malign lesions in the anogenital area must be carefully diagnosed and treated. An exactly defined algorithm with the final purpose to diagnose and remove for any length of time the papillomaviruses, as well as to protect the patients from any malign transformation does not exist for the time being. The therapies applied are frequently products of clinician’s individual approach and are purposed to eliminate the new formations induced by the viruses themselves. Adjuvant alternative therapy reducing the risk of early relapsing is not regularly applied. At the initial diagnosing of anogenital lesions of vague origin, the routine application of immuno-histochemical coloration according to Papanicolaou and PAN within the so called “golden standard”, determining the further clinic behavior is compulsory. The early surgical removal of lesions induced by the papillomaviruses and the application of prophylactic adjuvant therapy considerably reduce the risks of development of verrucous carcinoma, cervical carcinoma, Bowen carcinoma and planocellular carcinoma. Thus, the regular dermatological and venereal control and the interdisciplinary appraisal of the clinical status are of primordial importance. The local use of podophilotoxin in the form of solution or unguent is a widespread method of therapy of genital warts. Recently, some new, immunomodulatory substances are used, such as Imiquimod or Interferon. Good results are achieved in a number of patients by the systematic and local application of Cidofovir.
Key words: papillomavirus, condylomata, epidemiology, localization, diagnosis, treatment, Cidofovir, Interferon
Аddress for correspondence:
Georgy Tchernev, M. D., Department of Dermatology and Immunology, Municipal Hospital, Auenweg 38, 06847 Dessau, tel. 0049 1622643815 (GSM), e-mail: georgi_tchernev@yahoo.de


 Liver dysfunction and pregnancy  –  43, 2007, No 2, 25-34.
D. Petrova and K. Tchernev
Department of Propedeutics of Internal Diseases, Medical University -- Sofia

Summary: Liver diseases are rare complications of pregnancy, leading to delays in diagnosis and treatment. Most of the liver problems encountered in the pregnant patient are unique to pregnancy. The two most serious, acute fatty liver of pregnancy and HELLP syndrome (hemolysys, elevated liver enzymes, low platelets) are rare, whereas obstetric cholestasis, liver dysfunction associated with pre-eclampsia, and hyperemesis gravidarum are commoner. Acute fatty liver of pregnancy (AFLP) may begin innocuously with mild symptoms and liver enzyme abnormalities but, if left untreated, can progress to jaundice, liver failure and death in about 20% of the cases. The mortality rate for women with HELLP is about 1% to 3%, although rates as high as 25% have been observed. The perinatal mortality of infants is approximately 35%, depending on gestational age and the severity of the syndrome at the time of delivery. Obstetric cholestasis leads to premature births in up to 60%, fetal distress in up to 33%, and intrauterine death in up to 2% of patients. Knowledge of the patient’s gestational age is very helpful in the differential diagnosis of liver disease in pregnancy. Liver dysfunctions, associated with pre-eclampsia, AFLP and HELLP syndrome occur in the latter half (usually the third trimester) of pregnancy. Hyperemesis gravidarum begins in the first trimester, between weeks 6 and 12 of pregnancy. Cholestasis of pregnancy may begin in any trimester, but is more common in the second and third trimester. In HELLP syndrome, AFLP, and cholestasis of pregnancy, terminating the pregnancy is the treatment of choice, and may be lifesaving. To not miss these conditions, any liver disorder in a pregnant woman should be regarded as pregnancy-related until proven otherwise. Close medical and obstetric collaboration ensure low mortality.
Key words: pregnancy, liver dysfunction, AFLP- acute fatty liver of pregnancy, HELLP syndrome, hyperemesis gravidarum, оbstetric cholestasis, preeclampsia
Address for correspondence:
Assoc. Prof. Diana Petrova, Department of Propedeutics of Internal Diseases, 1, Sv. G. Sofiyski Str., Bg -- 1431, tel. +359 2 9230/654, fax +359 2 9239/ 654, GSM: +359 888 57 90 43, e-mail: doc_stefanova@abv.bg


 Modulating of renin-angiotensin-aldosterone system – new possibilities for primary and secondary prevention of atrial fibrillation – 43, 2007, No 2, 35-39.
D. Raev
Medical Institute, Ministry of Internal Affairs -- Sofia

Summary: The modern antiarrhythmic medications are not fully effective for rhythm control of atrial fibrillation (AF). This raises a need of alternative strategies. Nowadays, there are enough data, supporting the hypothesis for participation of local atrial inflammation in the pathophysiology of AF. The renin-angiotensin-aldosterone system plays an important role in the electrical and structural remodelling of the atria. ACE inhibitors and angiotensin receptor blockers may be the future substrate oriented medication for prevention and treatment of AF.
Key words: atrial fibrillation, ACE inhibitors, angiotensin receptor blockers, local atrial inflammation
Address for correspondence:
Assoc. Prof. D. Raev, M. D., Medical Institute, MIA, 79, Skobelev Blvd., Bg -- 1606 Sofia, tel. +359 2 9821326, е-mail: draevbg56@yahoo.com


 Proof and treatment of magnesium deficiency – 43, 2007, No 2, 40-42.
D. Yonova
Dialysis Clinic, Medical University Hospital “Aleksandrovska” -- Sofia

Summary: Magnesium is involved in the most cell functions and in the metabolism of the basic structural substances of the human body -- proteins, fats and carbohydrates. It is the second abundant human intracellular ion; the first one is potassium. The disturbances of magnesium metabolism influence the functions of almost all organs and systems, especially of those of vital importance -- the cardiovascular and the nervous system. Magnesium deficit predominates in the human pathology instead of magnesium intoxication. That was our reason to describe the ways of investigation of magnesium deficiency and its treatment.
Key words: magnesium deficit, hypomagnesemia, renal tubular excretion, cardiac arrhythmia, seizures, hypermagnesemia, magnesium supplementation
Address for correspondence:
Diana Yonova, M. D., Dialysis Clinic, University Hospital “Aleksandrovska”, 1, Sv. G. Sofiyski Str., Bg -- 1431 Sofia, tel. +359 2 92-30-463, 92-30-515, e-mail: dr_ionova@email.com


  Influence of drug formulation, food and circadian rhythms on drug bioavailability – 43, 2007, No 2, 43-50.
N. Petkova
Department of Clinical Pharmacology and Therapeutics, Medical University -- Sofia

Summary: To exert an optimal therapeutic action, an active moiety should be delivered to its site of action in an effective concentration for the desired period. This depends on the pharmacokinetic parameters of the active substance. The assessment of these pharmacokinetic characteristics includes testing of the delivering of the active substance to the systemic circulation. This is achieved by assessment of drug bioavailability, which of most drugs correlates with the clinical effect and therefore is an important pharmacokinetic effectiveness parameter. Drug formulation, food intake and circadian rhythms may influence drug bioavailability, leading to therapeutic failure or adverse drug reaction and toxicity by decreasing or increasing it. This article describes different oral drug formulations and their influence on bioavailability. The food-drug interactions are characterized and the resulting changes in the bioavailability are discussed. The influence of circadian rhythms on drug bioavailability is also typified.
Key words: bioavailability, drug formulation, food, circadian rhythms
Address for correspondence:
N. Petkova, M.D., Department of Clinical Pharmacology and Therapeutics, MHAT “Tsaritsa Ioanna”, 8, Byalo More Str., Bg -- 1527 Sofia, tel. + 359 2 9432152, e-mail: n.petkova@yahoo.com


 Adipobiology and adipopharmacology: new insights into biomedicine –  43, 2007, No 2, 51-56.
А. Tonchev(1), D. Dimitrov(2), R. Pancheva(3), M. Fiore(4), D. Kostov(5), Zh. Georgieva(5), L. Aloe(4) and G. Chaldakov(1)
(1)Division of Cell Biology, Medical University -- Varna
(2) Laboratory of Nutrigenomics, Medical University -- Varna
(3)Department of Pediatrics, Medical University -- Varna
(4)NGF Section, Institute of Neurobiology and Molecular Medicine, National Research Council -- Rome, Italy
(5)Department of Internal Medicine, Medical University -- Varna
Summary: Since the paradigm-shifting discovery of leptin in 1994, an increasing volume of basic and clinical data indicates that the adipose tissue, in both health and disease, is the body’s major endocrine and paracrine organ. In fact, under certain (e.g. obesogenic and inflammatory) conditions, more than 100 adipose-derived secretory proteins, named adipokines, are at present recognized. Adipokines have multiple biological functions beyond the regulation of lipid and charbohydrate metabolism (e.g. inflammation, immunity, feeding behavior, hemostasis, and lifespan). Adipokines thus play important roles in the pathogenesis of car­dio­me­tabolic and other obesity-related diseases. Conceptually, an emerging field of stu­dies in basic and clinical medicine examining adipose tissue biology is disignated adipobiology, whereas “adipopharmacology” connotes adipotargeting studies aimed at drug discovery. Here we highlight (i) some aspects of adipobiology and adipopharmacology of disease, (ii) our hypothesis of roles played by adipose-derived metabotrophic factors (adiponectin, nerve growth factor and interleukin-10 alike) in the pathogenesis and therapy of cardiometabolic disease, and (iii) at an adiponutrigenomic level, the emerging role of adipose tissue in controlling lifespan.
Key words: adipokines, metabotrophic factors, cardiometabolic disease, adiponutrigenomics, lifespan
Address for correspondence:
George Chaldakov, M. D., Division of Cell Biology, Medical Univesrity, 55, Marin Drinov Blvd., Bg -- 9002 Varna, tel. 052 754 394, 606 786, е-mail: chaldakov@yahoo.com



bullet 1'2007

Strain diversity and mechanisms of evolution of rotaviruses – 43, 2007, No 1, 5-13.
Z. Mladenova and N. Korsun
National Reference Enterovirus Laboratory, Department of Virology, National Center of Infectious and Parasitic Diseases -- Sofia
Summary: Human group A rotaviruses (RVs) are the major cause of severe dehydrating gastroenteritis in children under 5 years of age worldwide. The WHO data estimate annually in this age group that 20-70% of hospitalizations and 20% of fatal diarrhea cases occur due to severe rotavirus infection. Vaccination is current strategy to control and prevent rotavirus diarrhea, because improvement of hygiene and sanitization are not effective in focalization of the infection. During the last 10 years, the application of antigen characterization methods, reverse-transcription polymerase chain reaction and automated nucleotide sequencing confirmed that G1-G4 serotypes represent > 90% of circulating RVs G serotypes and allowed the identification of more than 42 distinct G-P combinations. Today, strain surveillance is a basis of the global programs for estimation of the RV burden and our understanding of probable mechanisms for viral evolution and disrtibution of new RVs strains. The development of RV vaccines is based on eliciting homotypic or heterotypic protection against one or more of the common G/P types. The introduction of 2 RV vaccines, licensed in the beginning of 2006, will require monitoring of circulating RV strains in each country and discovering of new globally or regionally RV types which are important activities for the success of RV vaccination programs. In this article, there are presented actual epidemiological information for the RV strain diversity in the world and Bulgaria as well as the possible mechanisms of viral evolution and emergence of new RV types.
Key words: rotavirus, serotype, genotype, RT-PCR, PAGE, reassortment
Address for correspondence:
Zornitsa Mladenova, Department of Virology, National Center of Infectious and Parasitic Diseases, 44A, Stoletov Blvd., Bg -- 1233 Sofia, tel. +359 2 831 00 42


Trace elements and uremia– 43, 2007, No 1, 14-16.
D. Yonova
Dialysis Clinic, University Hospital “Aleksandrovska” -- Sofia
The role of most of the trace elements in the development of uremia is not completely clear, but they do participate in a number of pathological processes, attending chronic renal failure: increased risk of cancer, anemia, cardiovascular disturbances, bone disease or immune deficiency. Undoubtedly, uremia changes serum levels of the trace elements differently, dependent on the stage of the chronic renal failure. The method of dialysis treatment has an important role as well, because of its different ability of elimination or importing of the trace elements, depending on the content of the dialysis solutions. Very little is known about the concentration of trace elements in healthy persons, and even less – in the uremic patients, so that every step towards the clarification of the problem deserves admiration.
Key words: uremia, trace elements, serum disbalance, accumulation
Address for correspondence:
Diana Yonova, M. D., Dialysis Clinic, University Hospital “Aleksandrovska”, 1, Sv. G. Sofiyski Str., Bg -- 1431 Sofia, tel. 9230463, 9230515, e-mail: dr_ionova@email.com


 Bioelectrical impedance for the assessment of body composition – 43, 2007, No 1, 17-20.
Zh. Boneva(1), P. Popivanov(2), M. Boyanov(2), N. Temelkova(2) and Vl. Hristov(2)
(1)Department of Endocrinology, Ministry of the Interior – Medical Institute -- Sofia
(2)Clinic of Endocrinology, University Hospital “Alexandrovska” -- Sofia
This review discusses the principles, methods and indications for application of bioelectrical impedance (BIA( in clinical practice. BIA is а widely used method for estimating body composition. The technology is relatively simple, quick and noninvasive, portable аnd non expensive. BIA is currently used in diverse settings, including private clinician offices, health clubs and hospitals. The data from various studies in healthy and ill subjects suggest that BIA works well in healthy subjects and patients with stable water electrolyte balance and with validated BIA equation that is appropriate with regard to age, sex, and race. The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed in 2004 the guidelines for the clinical use of BIA measurements. It reviews the current applications, limitations and recommendations for use of the method in clinical settings.
Key words: bioelectrical impedance, body composition, fat mass, obesity
Address for correspondence: Zhivka Boneva, Department of Endocrinology, Ministry of the Interior -- Medical Institute, 75, Gen. Skobelev Blvd., Bg -- 1606 Sofia, tel. +359 2 9821351


 Current use of nitroimidazoles in clinical practice, mechanism of action and diagnostics of bacterial susceptibility – 43, 2007, No 1, 21-31.
L. Boyanova(1), R. Kolarov(2) and I. Mitov(1)
(1)Department of Microbiology, Medical University -- Sofia
(2)University Hospital of Maxillo-Facial Surgery -- Sofia
Nitroimidazoles are bactericidal prodrugs targeting bacterial DNA and they are used in the treatment of anaerobic infections (involving Clostridium difficile-induced colitis and bacterial vaginosis), infection with protozoans as well as Crohn's disease. Activities of metronidazole (MTZ) and tinidazole are similar. Most clinically significant anaerobes remain MTZ susceptible, although resistance has been reported in Bacteroides fragilis group, clostridial species and anaerobic cocci, and in about 1/2 of non-sporeforming Gram-positive anaerobic rods. However, the susceptibility of anaerobic species to MTZ is not always predictable. Advantages of MTZ are the high activity against Gram-negative anaerobes, availability for oral and intravenous application, rapid bacterial killing, good tissue penetration, low risk for inducing C. difficile colitis, and low cost. The mutagenic activity of the MTZ in bacterial systems and animals motivates wider and longer studies on the genotoxicity in humans. Bacterial susceptibility testing to MTZ has specific requirements. MTZ is considered the gold standard agent, against which newer anaerobic antibiotics are compared. Triple regimen, involving MTZ, is an alternative for H. pylori eradication, and MTZ is recommended in the quadruple regimens in case of unsuccessful eradication. Although primary H. pylori resistance rate to MTZ is 20-40% in Europe, the agent is active against 2/3 of the resistant H. pylori strains. The mechanisms and genes for nitroimidazole resistance have been evaluated. Nitazoxanide, a new nitroimidazole-like drug, could have a good therapeutic potential.
Key words: nitroimidazoles, metronidazole, anaerobes, Helicobacter pylori, resistance, clinical application
Address for correspondence:
Assoc. Prof. Ludmila Boyanova, Department of Microbiology, Medical University, 2, Zdrave Str., Bg -- 1431 Sofia, tel. +359 2 91-72-730, e-mail: lboyanova@hotmail.com


Assessment of subclinical аtherosclerosis in patients with renal failure – 43, 2007, No 1,  32-37.
M. Lubomirova
Clinic of Nephrology, University Hospital “Alexandrovska” -- Sofia
Summary: A number of factors contributе to the increased prevalence of cardiovascular disease in patients with chronic renal failure. The atherogenic risk can be evaluated with non-invasive methods by measuring the intima-media thickness of the common carotid artery as well as by Doppler ultrasound of the renal vessels. The changes of both parameters are considered an marker of initial atherosclerosis, i.e. subclinical atherosclerosis.
Key words: cardiovascular disease, cardiovascular risk factors, chronic renal failure, intima-media thickness, renal Doppler ultrasound
Address for correspondence:
M. Lubomirova, M. D., Clinic of Nephrology, University Hospital “Alexan­drovska”, 1, Sv. G. Sofiyski Str., Bg -- 1431 Sofia, e-mail: MLjubomirova@yahoo.com



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