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Vol. 44, 2008



Chronobiology of nocturnal asthma
M. Yankova and S. Filchev

Pediatric Clinic, MHAT “Alexandrovska” -- Sofia
Summary: Nocturnal asthma is defined as an exacerbation of the underlying asthma condition at night, with usual peak expiratory flow variability of at least 20%. Approximately two-thirds of asthmatics suffer nighttime symptoms. The underlying mechanism likely involves endogenous circadian rhythms acting on the hyperreactive bronchi of people with asthma. Although patients with more severe asthma often have nighttime symptoms, nocturnal asthma may have some unique features. A chronotherapeutic approach, in which corticosteroids, long-acting beta-agonists, theophylline, leukotriene modifiers and anticholinergic medication are administered at specified times during the day, may enhance response to therapy. An increased understanding of circadian rhythms and their impact on nocturnal asthma should ultimately lead to the development of novel therapeutic strategies.
Key words: nocturnal asthma, chronobiology, chronotherapy, inflammation
Address for correspondence: Milena Yankova, M. D., Pediatric Clinic, MHAT “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg -- 1431 Sofia, tel. +359 2 9230 359


Recent progress in hepatitis B viral infection knowledge. Acute viral hepatitis B. Etiological and pathogenetical aspects
I. Baltadzhiev, N. Popivanova and O. Boykinova
Department of Infectious Diseases, Clinical Parasitology and Tropical Medicine, Medical University -- Plovdiv
Summary: The knowledge of HBV infection augments progressively, and changes our point of view towards the natural history of this infection. It contributes to the battle against the infection and to the prevention of its dangerous consequences. This review focuses on the acute viral hepatitis B recent scientific progress and points to the peculiarities in the HBV replication cycle, the viral genotypes and emerging viral mutants. The nonspecific and specific cellular and humoral immune responses, as well as the immunological memory and protective immunity are discussed. The role of viral proteins, CTL responses, the cytokine effects and liver cell apoptosis mechanisms in fulminant hepatitis B are presented.
Key words: acute viral hepatitis B, HBV proteins, genotypes and viral mutants, immune response, non-cytolytic downregulation of viral replication, fulminant hepatitis B, cytokine effects, hepatocellular apoptosis
Address for correspondence: I. Baltadzhiev, M. D., Department of Infectious Diseases, Clinical Parasitology and Tropical Medicine, Medical University, 15A, Vasil Aprilov Blvd., Bg -- 4000 Plovdiv


Fibroblast growth factor 23 -- a phosphate-regulating substance
D. Yonova(1) and R. Boneva(2)
(1)Clinical Center of Hemodialysis, UMHAT “Alexandrovska” -- Sofia, (2)Clinic of Nephrology and Hemodialysis, UMHAT “G. Stranski” -- Pleven
Summary: Circulating fibroblast growth factor 23 (FGF23) increases renal phosphate excretion and decreases bone mineralization. It might be a secondary effect of phosphate elimination of the kidney or a direct action on the fibroblast growth receptor-1 in bones of the human skeleton. FGF23 is produced by the osteoblasts and its main function in healthy persons is to inhibit natrium-coupled reabsorption of inorganic phosphate in the renal proximal tubule. It has been proved that FGF23 levels are increased in dialysis patients, but still it is not clear if the higher serum levels are involved in any pathophysiologic effect or the phenomenon is only some kind of compensatory reaction.
Key words: fibroblast growth factor 23, renal phosphate excretion, dialysis pa­ti­ents, chronic renal failure
Address for correspondence: Assoc. Prof. Diana Yonova, M. D., UMHAT “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg – 1431 Sofia, tel. +359 2 9230463, e-mail: dr_ionova@email.com


Silymarin in the clinical practice
D. Petrova and K. Tchernev
Clinic of Gastroenterology, Department of Propaedeutic of Internal Diseases, Medical University -- Sofia
Summary: The healing power of silymarin has been known since ancient times (Theophrastus; 4th century BC). Silymarin is extracted from the milk thistle (Silybum marianum). Eighty percent of the plant extract are represented by Silibinin. Silymarin prevents liver damage and helps maintain normal liver function, possibly due to its antioxidant and membrane-stabilizing properties. Silymarin (Carsil -- Sopharma) increases intracellular gluthation and prevents the oxidative stress in hepatocytes by decreasing toxic superoxide radicals and nitric oxide production. This alleviates liver damage caused by hepatotoxins and prevents the progression of liver damage, including liver damage caused by alcohol consumption, into liver cirrhosis. Silymarin has been found to protect hepatocytes against a number of hepatotoxic drugs, including acetaminophen, dilantin, phenothiazine, halothan, and methotrexate. It can be used effectively as an antidote if applied in high doses (3400 mg/daily) up to the 48th hour from mushroom poisoning with Amanita phalloides. Silymarin stops the fibrogenesis in the liver by inhibiting the activity of the stellate cells and their transformation into myofibroblasts as well as the deposition of collagen and laminin in the subendothelial space of the synosoids. Silymarin, overall, has a strong immunostimulatory effect by increasing lymphocyte proliferation and stimulating the production of INF-gamma, IL-4, and IL-10. The standardized extract (MK-001) in vitro supresses the infection of liver cells with Hepatitis C Virus. Patients with hepatitis C who take silymarin are enjoying better physical, psychological and sexual activity than those who do not take silymarin. The protective effects of silymarin can be used in cancer patients as an adjunct to established therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. When applied in higher doses, silymarin also reduces the level of the prostate-specific antigen in patients with prostate cancer following prostatectomy and radiotherapy. Silymarin is effective in the treatment of diabetes mellitus as it normalizes HbA(1)c, fasting blood sugar levels, overall cholesterol, LDL, and triglycerides.
Key words: silymarin, phytotherapy, antioxidants, hepatoprotection
Address for correspondence: Assoc. Prof. Diana Petrova, M. D., Clinic of Gastroenterology, UMHAT “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg -- 1431 Sofia


Complex cardiac rehabilitation as secondary prevention of cardiovascular diseases
S. Kemerov
Department of Physical Medicine and Rehabilitation, University Hospital “Lozenets” -- Sofia
Summаry: This article treats some issues of cardiac rehabilitation as secondary prevention of cardiovascular diseases. This pathology is all too often and some social problems persist with their heavy consequences. The need of multidisciplinary approach to resolve these problems arises. Some discussion of necessary result-oriented measures and their organization for a more effective health policy is made.
Key words: cardiac diseases, cardiac rehabilitation, exercise
Address for correspondence: Stoyan Kemerov, M. D., Department of Physical Medicine and Rehabilitation, University Hospital “Lozenetz”, 1 Kozyak Str., Bg -- 1407 Sofia, e-mail: kemerov_stoyan@yahoo.com






Cystic neoplasms of the pancreas -- what the clinician should know? – 44, 2008, No 3, 5-12.
A. Hilendarov, K. Velkova and N. Traykova
Department of Diagnostic Imaging, MU -- Plovdiv
Summary: Primary cystic neoplasms of the pancreas (serous, mucinous and intraductal) are lesions of emerging importance. With the wide availability of modern imaging methods (computed tomography, ultrasound tomography, magnetic resonanсе imaging and invasive procedures under imaging control), these neoplasms are being recognized with increasing frequency. It is often possible to differentiate cystic neoplasms preoperatively not only from other cystic pancreatic lesions (such as pancreatic pseudocysts) but also from one another. This differentiation is very important for the clinicians, since these neoplasms have radically different biologic behavior. The purpose of this survey is to illustrate the spectrum of imaging findings of cystic pancreatic lesions and highlight the role, advantages, and limitations of various imaging modalities in the differential diagnosis of pancreatic cystic neoplasms.
Key words: pancreatic cystic neoplasms, methods of diagnostic imaging
Address for correspondence: 
A. Hilendarov, M. D., 49 Volga Str., ap. 14, Bg -- 4002 Plovdiv, e-mail: dr_hill@abv.bg


Vascular endothelium -- diagnosis of endothelial dysfunction – 44, 2008, No 3, 13-17.
D. Yonova(1) and R. Boneva(2)

(1)Clinical Center of Hemodialysis, Medical University -- Sofia, (2)Clinic of Nephrology and Hemodialysis, Medical University -- Pleven
Summary:  Vascular endothelium is a thin monocellular layer covering internal surface of the vascular system, separating the blood from the vessels. The endothelium serves as a receptor-effector organ and reacts to all physical or chemical stimuli by delivering vasoactive substances, regulating vascular tone and blood-tissue homeostasis. The endothelium has not only exocrine, but also endocrine and paracrine functions. The oxidative stress, attending a number of diseases, leads to endothelial dysfunction and inflammation of the vessels. The endothelial dysfunction may serve as an independent risk factor of vascular diseases. There are sufficient data to conclude that the methods for evaluating the endothelial function are suitable and appropriate in the clinical practice for diagnosis and follow up of the development of the diseases. Most of them are not invasive and are safe for the patients that makes them preferable.
Key words:  endothelial dysfunction, vascular disease, vascular tonus, nitric oxid vaso­di­la­ta­tion, pletismography
Address for correspondence
: Assoc. Prof. Diana Yonova, M. D., Clinical Center of Hemodialysis, UMHAT “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg -- 1431 Sofia,  tel. +359 2  9230463, e-mail: dr_ionova@email.com


Adverse effects and interactions of herbal medicines – 44, 2008, No 3, 18-23.
R. Radev and K. Sokolova

Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Thracian University -- Stara Zagora
Summary:  Opposing to the commonly adopted idea, the use of herbal remedies can pose a serious risk of development of adverse effects and interactions between herbal remedies and conventional drugs. The adverse effects and interactions between some popular herbs (Hypericum perforatum, Ginkgo biloba, Ginseng, Echinacea) and frequently used drugs (cardiovascular, nonsteroidal antiinflammatory drugs, antidepressants) have been discussed. Better physician awareness is required to minimize the risk of herbal products’ adverse effects and herb-drug interactions. Physicians need to ask questions about the use of herbal products as part of the medication history. Моre rigorous regulations of alternative medicines are required.
Key words:  herbal remedies, Hypericum perforatum, Ginkgo biloba, adverse effects, interactions
Address for correspondence:
Kameliya Sokolova, Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, 11, Armeiska Srt., Bg -- 6000 Stara Zagora, tel. +359 42 664310, e-mail: camel56@abv.bg





Progressive multifocal leucoencephalopathy in autoimmune rheumatic diseases: clinical patterns, diagnostics and therapy – 44, 2008, No 2, 5-12.
St. Kuzmanova and P. Solakov

Clinic of Rheumatology, University Hospital “Sv. Georgi”--Plovdiv
Summary: Тhе progressive multifocal leucoencephalopathy (PML) (synonyms: progressive multifocal leukodystrophy, multifocal demyelinating disease) may complicate immunosuppressive state of rheumatic diseases. PML is a progressive fatal demyelinating disorder with oligodendroglial infection by thе human papova virus JC. PML typically presents with focal subcortical neurological deficit. A limited number of reports in the world literature describe association of PML with SLE, Wegener’s granulomatosis, overlap syndrome, Behсet’s syndrome and systemic sclerosis. In these cases with PML there is no evidence of significant activity of the rheumatic disease and MRI reveals no signs of CNS vasculopathy. Highly active immunosuppressive treatment of patient with PML and with altered cell-mediated immunity is followed by rapid neurological decompensation and new florid MRI imaging changes. MRI findings are characteristic in PML with a high T2 signal and low T1 signal. CSF identification of JC virus by polymerase chain reaction has sensitivity of 95% and specificity of 99%. Recent reports show improved PML outcome following aggressive, highly active antiretroviral therapy.
Key words: progressive multifocal leucoencephalopathy, lupus erythematosus systemicus, JC viruses, polyomavirus
Address for correspondence:
Prof. Stefka Kuzmanova, MD, UMHAT ”Sv. Geogi”, 15-A, Vassil Aprilov Str., Bg--4002 Plovdiv, tel. +359 32 602 532, e-mail: stef53kuz33@yahoo.com


Foodborne and waterborne viral infections – 44, 2008, No 2, 13-18.
N. Korsun(1), Z. Mladenova(1) and P. Teoharov(2)

(1)National Enterovirus Laboratory, (2)National Hepatitis Viruses Laboratory, National Center of Infectious and Parasitic Diseases --Sofia
Summary: Human enteric viruses are the leading cause of foodborne and waterborne infections. Different groups of viruses may cause illness after ingestion of contaminant food/water. In this article, the main routes of food products contamination are presented. The main groups of foodborne and waterborne viral agents, their properties, persistence; the epidemiology, clinic manifestations and control of diseases are reviewed.
Key words: foodborne/waterborne viruses, shellfish, hepatitis A virus, noroviruses
Address for correspondence: N. Korsun, M. D., National Enterovirus Laboratory, National Center of Infectious and Parasitic Diseases, 44A Gen. Stoletov Blvd., Bg -- 1233 Sofia, e-mail: polionl_nk@abv.bg


Role of catecholamines and metanephrines as biochemical markers in tumor diseases – 44, 2008, No 2, 19-23.
L. Mateva and V. Mitev

Laboratory of Cell Signaling, Department of Chemistry and Biochemistry, Medical University – Sofia
Summary: Catecholamines -- norepinephrine, epinephrine and dopamine are biologically active substances that have various regulatory functions in cells. Norepinephrine and epinephrine are neurotransmitters, closely related with the etiology of different physiologic and neurodegenerative diseases of the central nervous system. This gives rise to the significance of determining the levels of catecholamines and their metabolites -- e.g. normetaepinephrine and metanephrine, in tissue sample, serum and urine, which can serve as biochemical markers for a number of diseases (pheochromocytoma, Parkinson’s disease, Alzheimer, and others).
Key words: catecholamines, norepinephrine, epinephrine, dopamine, metanephrines, normetaepinephrine, metanephrines, biochemical markers
Address for correspondence:
Lyudmila Mateva, Department of Chemistry and Biochemistry, Medical University, 2 Zdrave Str., Bg -- 1431 Sofia, e-mail: lmateva@medfac.acad.bg


Idiopathic nocturnal leg cramps in the elderly – 44, 2008, No 2, 24-29.
К. Kostov and Iv. Petrov

Medical Institute, Ministry of Interior--Sofia
Summary: Nocturnal leg cramps are common in older people. Although cramps are generally a benign and transient problem, they can cause considerable distress for patients. Management can be difficult, but they also may be a symptom of many common diseases and medications. Identification of potentially treatable factors is important in patients with cramps. Physiological methods may be useful for preventing cramps in some people, but there have been no controlled trials of these approaches. Quinine is moderately effective in preventing nocturnal leg cramps. However, there are concerns about the risk/benefit ratio with this drug. Vasodilators and anticholinergic medicines show a good effect in controlled trials. The application of vit. E and magnesium has a controversial effect. The use of verapamil, gabapentin and a combination of vit. D and calcium may be an alternative treatment, but there are no controlled trials, proving the effect of these medicines.
Key words: muscle cramps, elderly, treatment
Address for correspondence: K. Kostov, M. D., Ph. D, Clinic of Neurology, Medical Institute of Ministry of Interior, 79 “Scobelev” blvd., Bg -- 1606 Sofia, Phone: +359 2 9821576, Fax: +359 2 9531235, e-mail: drkostov@netissat.bg


Effect of physical activity on cardiovascular function in childhood and adolescence adolescence – 44, 2008, No 2, 30-35.
R. Nikolova

National Center of Public Health Protection--Sofia
Summary: Regular physical activity is an integral component of health status that is necessary to be formed in the period of childhood of each individual. Significant goal for introducing physical activity in the school and occupational environment is its influence for improving health and physical status, increasing of individual’s performance, effect on the cardiovascular and other systems. Results concerning the effect of physical activity on cardiovascular function are summarized. Recent studies reveal that 30-minutes moderate physical activity during the week has a significant effect on prevention of cardiovascular and other chronic diseases. Results of Bulgarian and international studies show the necessity of programs for promoting physical activity in order to reduce morbidity rates in children and adolescents.
Key words: physical activity, cardiovascular function, childhood, adolescents
Аddress for correspondence:
Rouja Nikolova, M. D., Laboratory of Physiology and Ergonomy, National Center of Public Health Protection, 15, Acad. Ivan Geshov Str., Bg -- 1606 Sofia, tel. +359 2 8056 207, e-mail: rouja_n@yahoo.com





Lichen ruber planus: Тhe undiscovered way from infection to autoimmunity – 44, 2008, No 1,    5-13.
G. Tchernev(1), M. D. Apostolova(1), Y. Georgieva(2), M. Dikova-Tcherneva(3), A. Kotzev(4) and A. Zhelyazkov(5)
(1)Department of Molecular and Cell Biology, Bulgarian Academy of Sciences -- Sofia
(2)Medical University -- Rostock, Germany
(3)Department of Physiotherapy, University Hospital “Tsaritsa Ioanna” -- Sofia
(4)Department of Internal Diseases and Gastroenterology, University Hospital “Alexandrovska” -- Sofia
(5)Department of Dermatology and Venereology, University Hospital “Alexandrovska” -- Sofia
Summary:  The pathogenetic chains taking place in the induction of lichen ruber and its subforms have always been subject to vivid discussions which have not found a definitive solution yet. The immunological pathogenetic cascade provoking typical lichenoid infiltrates includes not only the activation of CD4+ and CD8+ T-cells, but also the secretion of interferon-gamma and the expression of ICAM-1 and FAS-L from the keratinocytes in the epidermal layer of the skin. The further T-cellular mediated apoptous reaction induces the typical clinic morphology of lichen ruber with its characteristic, violet papules. The large-scale morphologic picture in patients suffering from lichen ruber probably represents an alarming signal for possible disorders in the tissue homeostasis. We suggest that the development of the different forms of lichen ruber is the final effect of antigenic mimicry events with exogenic character, which occur during disturbed inner homeostasis or inadequate maintenance systemic and local therapy. Recurrent infections and multimedication are probably the cause for immune response expansion towards the cutaneous structures imitating or exhibiting close morphology to bacterial, fungal or viral structural elements. Within the primary destructive inflammatory processes, unmasking of proteins in the area of the skin happens and preconditions are indirectly created for the extension of the immune response and, consequently, for the development of heterogenic clinic picture as well.
Key words:  autoimmunity, infection, lichen ruber planus
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


Biochemistry of apoptosis – 44, 2008, No 1,  14-19.
B. M. Mihov
Department of Chemistry and Biochemistry, Faculty of Medicine, Sofia University „Sv. Kliment Ohridski”
Summary: The biochemistry of apoptosis -- the programmed cell death, is described. The molecular mechanisms of the intracellular and extracellular signals for apoptosis are observed, stressing on the role of caspases in executing of this process. Both ways of appearing of the extracellular apoptosis are represented. The noncaspased apoptosis is also described. The mechanisms of the apoptosis bodies removing are also discussed.
Key words:  apoptosis, caspases, TNF, Fas, T-lymphocytes, macrophages
Address for correspondence:  Assoc. Prof. Budin M. Michov, MD, DSc, 47, Ilarion Dragostinov, Bg  --  1505 Sofia, Tel./ Fax 9713047, bmichov@dir.bg


Drug-induced hyperthermic syndromes – 44, 2008, No 1,  20-26.
R. Nikolov and Kr. Yakimova
Department of Pharmacology and Toxicology, Faculty of Medicine, Medical University -- Sofia
Summary:  A variety of drugs, chemical substances, and toxins may disrupt thermoregulation in children and adults. Specifically, drugs that affect serotonin, acetylcholine, dopamine, and norepinephrine are associated with various hyperthermic syndromes. Severe hyperthermia (body temperature > 40-41 degrees centigrade) may cause brain damage and multiorgan failure, including rhabdomyolysis, renal failure, and coagulopathy. Hyperthermia may be treated rapidly by cooling measures to avoid serious complications. Antipyretic medications are not effective in drug-induced hyperthermia (some antipyretic drugs, such as salicylates, may worsen hyperthermia). Excessive heat production related to agitation or increased muscle rigidity can be controlled with benzodiazepines and dantrolene.
Key words:  hyperthermia, serotonin syndrome, neuroleptic malignant syndrome, malignant hyperthermia
Address for correspondence:  Rumen Nikolov, M.D., Department of Pharmacology and Toxicology, Faculty of Medicine, Medical University, 2 ”Zdrave” str., Bg  --  1431 Sofia, tel.  +359 2 91 72 622, e-mail: ru_nikolov@abv.bg


QT interval dispersion -- study method and significance – 44, 2008, No 1, 27-31.
I. Simova and S. Denchev
Clinic of Cardiology, University Hospital “Alexandrovska”  --  Sofia
Summary: The QT interval dispersion is a global marker of the variability of the process of repolarization of ventricular myocardium. It is derived from a 12-lead standard surface electrocardiogram with a precise determination of the QT interval of all 12 leads. The aim of our presentation is to delineate the difficulties in QT interval measurement and the methods for QT interval dispersion calculation. We look further on the prognostic significance of this marker in regard to cardiac and all-cause death as well as its significance in the subgroups of patients with an increased risk of coronary atherosclerosis and already clinically apparent ischemic heart disease.
Key words:  myocardial repolarization, QT interval, dispersion prognostic value, study method
Аddress for correspondence:  Iana Simova, M. D., Clinic of Cardiology, University Hospital “Alexandrovska”, 1, Sv. G. Sofiyski Str., Bg  --  1431 Sofia, email: ianahr@yahoo.com


Small heat shock proteins and their role in human diseases – 44, 2008, No 1, 32-42.
K. Petkova(1), K. Todorova-Ananieva(2) and M. Stamenova(1)
(1)Institute of Biology and Immunology of Reproduction -- Bulgarian Academy of Science
(2)SHATOG “Maychin dom” -- Sofia
Summary:  Small heat shock proteins (MW is approximately 12-43 kDa) share significant sequence similarity within the "alpha-crystallin domain" but exhibit different patterns of gene expression, transcriptional regulation, sub-cellular localization, and function. Monomers of sHSP assemble into dynamic oligomers which undergo subunit exchange and they bind a wide range of cellular substrates. As molecular chaperones, the sHsps protect protein structure and activity, thereby preventing disease, but they may contribute to cell malfunction when perturbed. For example, sHsps prevent cataract in the mammalian lens. On the other hand, mutated sHsps are implicated in diseases such as congenital cataract, desmin-related myopathy and they have a relationship to neurological disorders including Parkinson's and Alzheimer's disease.
Key words:  small heat shock proteins, cataract, desmin-related myopathy, ischemia, neurological diseases
Address for correspondence:  K. Petkova, Institute of Biology and Immunology of Reproduction “Acad. K. Bra­tanov” -- Bulgarian Academy of Science, 73 Tzarigradsko shosse, Bg  --  1113 Sofia, e-mail: kameliya_vinketova@abv.bg


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About the Journal Current Issue Archive Review Articles Original Papers Case Reports Requirements to the Authors Editorial Board Contacts CML Home