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Review articles

Volume 42, 2006




Sarcopenia – the new pandemic - 42, 2006, No 4, 5-9.
Zh. Boneva

Department of Endocrinology, Ministry of the Interior – Medical Institute - Sofia
Summary: Sarcopenia is a term widely used to describe the slow, but progressive loss of muscle mass and strength with advancing age. Prevalence increases from 13-24% in persons under 70 years of age to > 50% in those over 80 years of age. This review discusses current concepts of the pathogenesis, treatment, and prevention of sarcopenia. The etiology of sarcopenia is still unclear but several important factors have been identified. Neurological, metabolic, hormonal, nutritional, and physical activity-related changes with age are likely to contribute to the loss of muscle mass. Exercise intervention can prevent and even reverse the muscle atrophy associated with aging.
Key words:  sarcopenia, muscle strength, muscle mass, elderly
Address for correspondence: Zhivka Boneva, Department of Endocrinology, Ministry of the Interior - Medical Institute, 79, Gen. Skobelev Blvd., Bg; 1606 Sofia, tel. +359 2 9821351, +359 888 643 843


Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) -42, 2006, No 4, 10-15.
D. Dimov and I. Zhutev

Rheumatological Department, Military Medical Academy - Sofia
Summary:  Kikuchi-Fujimoto disease is a rare illness, characterized by lymphadenopathy, general symptoms and extranodal manifestations. Etiology and pathogenesis are unclear. The clinical features can suggest infectious, autoimmune or malignant systemic diseases. The diagnosis is based on the lymph node biopsy data establishing necrosis and histiocytic infiltration without neutrophils. The course is as a rule benign self-limiting, however, some fatal cases are described. Corticosteroid therapy is indicated in cases with severe, generalized lesions, but all patients need close follow-up for several years because someone may develop an autoimmune disease.
Key words:  Kikuchi-Fujimoto disease, etiopathogenesis, clinical features, diagnosis, prognosis
Address for correspondence:  Prof. Detelin Dimov, Rheumatological Department, Military Medical Academy, 3, Sv. Georgi Sofiiski Str., Bg – 1606 Sofia, tel. +359 2 922 57 35


Perivascular adipose tissue – meaning for structure, function and pathology of the vascular wall - 42, 2006, No 4, 16-20.
E. Lakova(1) and G. Krasteva(2)

(1)Department of Biology and Pathophysiology
(2)Department of Experimental and Clinical Pharmacology
Medical University – Pleven
Summary: Virtually all blood vessels are surrounded by perivascular white adipose tissue (pWAT). The quantity of this fat elevates with diet-induced obesity and aging. The excess of pWAT contributes to the increased vascular stiffness. Moreover, pWAT releases vasodilators and vasoconstrictors, and impairs the balance of vasoactive substances by producing insulin resistance in obesity. The result is increased vascular tone – crucial factor for coronary vasospasm and arterial hypertension. The cytokines, chemokines, growth factors and other biologically active molecules secreted by pWAT exert paracrine action, “outside-to-inside” on vascular wall. In this way pWAT contributes to structural changes in atherosclerosis and restenosis after balloon injury. Very little is known about regulation of secretory processes in pWAT, the interaction with the other obesity-related risk factors and rational approaches to treatment.
Key words:  perivascular adipose tissue, adipokines, vascular tone, atherosclerosis
Address for correspondence:  Emilia Lakova, M. D., Department of Pathophysiology and Biology, Medical University,1 Sv. Kl. Ohridski Str., Bg 5800 Pleven, tel. +359 64 884 273, +359 64 884 252 e-mail:


Intraoperative complications during oncogynecological surgery -  42, 2006, No 4, 21-23.
Y. Kornovski

Gynecological Clinic, MHAT ,,Sv. Anna”, Medical University – Varna
Summary:  In the present review, the most common intraoperative complications occurring during surgery in women with gynecological cancer as well as the causes leading to them are discussed. The methods and tecniques for the management of these complications are presented.
Key words:  intraoperative complications, gynecologic surgery
Address for correspondence:  Iavor Dimitrov Kornovski, M. D., 39 Chaika, apt. 51, Bg – 9010 Varna, tel./fax +359 52 31-24-15, GSM: +359 887-62-47-50


The role of eosinophil cationic protein in the assessment of bronchial asthma in children – 42, 2006, No 4, 24-27.
S. Mileva and I. Galeva
Clinic of Pediatrics, University Hospital "Alexandrovska" – Sofia
Summary:  Eosinophils are known to be an indirect marker of airway inflammation in asthma. It is well known that the total eosinophil count reflects asthmatic activity and is useful for regulating steroid dosage and for early detection of exacerbations. Eosinophils are currently regarded as the effector cells contributing to much of the asthma pathology. Eosinophil-mediated damage to the respiratory epithetlium is a major pathogenetic mechanism in asthma. Activated eosinophils are able to release cytotoxic proteins, one of them is the eosinophil cationic protein (ECP). Measurement of ECP is helpful in determining asthma activity and monitoring antiinflammatory therapy.
Key words: asthma, eosinophils, eosinophil cationic
Address for correspondence:Sirma Mileva, M.D., Clinic of Pediatrics, University Hospital "Alexandrovska", 1, Sv. G. Sofiiski, Blvd., Bg - 1431 Sofia, e-mail:


Common problems in the surgical treatment of cutaneous melanoma – 42, 2006, No 4, 28-37.
G. Tchernev

Department of Dermatology and Immunology, Municipal Hospital - Dessau, Academic Educational Hospital of the Martin-Luther-University - Halle-Wittenberg, Germany
Summary:  When a melanoma suspicious lesion requires diagnosis, the skin biopsy is the single most important test. Information contained in the biopsy will determine management and prognosis of the patient. For åvery skin lesion which is clinically highly suspicious for melanoma and small enough to be excised, surgical excision is recommended. An elliptical scalpel excision, oriented parallel to the direction of a possible reexcision, should take into account cosmetic or functional factors and should not change the subdermal lymphatic ways which drain in a proximal direction. A biopsy of any suspicious skin lesion must be planned with possibility of future treatment in mind. The incisions should be always well thought out and an excisional biopsy should be performed if possible to allow the pathologist to examine the entire lesion. Curretage and shave biopsy have no place in the diagnostic and treatment of suspicious skin lesions. If some of the lesions are too large to allow excisional biopsy, a punch or incisional biopsy incorporating normal tissue is adequate. The treatment of choice of primary skin melanoma is the surgical excision. The appropriateness of margin size in melanoma surgery has changed over time from an aggressive to a more conservative approach. For melanoma in situ, surgical incision with 5 millimeter margin of clinically normal skin is considered adequate. Smaller margins will result in corresponding increase in local recurrence. For skin melanoma till 2 millimeter in thickness, a 1 centimeter margin is adequate and for melanoma of more than 2 millimeter in thikness, a minimum of 2 centimeter margin is adequate.
Key words:  melanoma, surgical treatment, local recurrence, tumor thickness, field cells
Address for correspondence:  Georgi Tchernev, M.D., Department of Dermatology and Immunology, Munici-pal Hospital, Auenweg 38, 06847 Dessau, tel. 0049 340 501 4050/4056, e-mail:


Schizophrenia and autoimmunity - 42, 2006, No 4, 38-43.
S. Dimova

Department of Pathophysiology, Faculty of Medicine, Thracian University - Stara Zagora
Summary: Schizophrenia affects 1% of the population worldwide, but its etiology remains obscure. Numerous theories have been proposed regarding the cause of schizophrenia, ranging from developmental or neurodegenerative processes or neurotransmitter abnormalities to autoimmune mechanisms. In this review recent findings suggestive of involving of an autoimmune process in the etiology of schizophrenia are examined. Associations with various autoimmune diseases, increased levels of autoantibodies, altered in vivo and in vitro levels of cytokines, influence of immunosuppressive and anticytokine therapy suggest that, in some patients at least, autoimmune mechanism could play a role in the development of disease.
Key words:  schizophrenia, autoimmunity, autoantibodies, cytokines, immunomodulation
Address for correspondence:  Svetlana Dimova, M.D., Department of Pathophysiology, Faculty of Medicine, 11, Armeiska Str., Bg 6003 St. Zagora, e-mail:





Influence of cigarette smoking on thyroid-associated ophthalmopathy, thyroid function and autoimmunity - 42, 2006, No 3, 5-8.
J. Matrozova
(1) and M. Boyanov(2)
(1)Clinic of Hypophyseal-Adrenal and Gonadal disorders, Endocrinology and Gerontology Hospital "Akad. Iv. Penchev"
(2)Endocrinology Clinic, University Hospital "Alexandrovska" Medical University - Sofia
Cigarette smoking is an important cause of increased morbidity and mortality in developed countries, and it is a social problem, also concerning the Bulgarian population. Cigarette smoke contains a variety of chemical compounds, including numerous toxic substances (carcinogens, thyocianate, nicotine). Smoking increases the risk of autoimmune thyroid diseases, such as Graves' disease, thyroid-associated ophthalmopathy, Hashimoto's thyroiditis. The mechanisms by which smoking affects thyroid gland are not fully understood. In healthy adults, smoking has either a weak stimulatory or no effect on thyroid function and size. There are several mechanisms by which smoking affects thyroid hormone levels that include the stimulatory effect of thyocyanate in combination with the other ingredients in cigarette smoke, like 2-3 hydroxypiridine. In patients with subclinical hypothyroidism, smoking leads to increased levels of TSH and worsening of the biochemical markers. Smoking is a major risk factor for the development of
Graves ophthalmopathy. The mechanisms include direct irritative effects, immunomodulatory changes, stimulation of the cytokine effect, change in the TSH receptor structure, changes in the levels of interleukin-1-receptor antagonist. Smoking is found to be negatively associated with thyroid cancer.
Key words: thyroid gland, tobacco smoking, autoimmune disease, function
Address for correspondence:
Mihail Boyanov, M.D., Endocrinology Clinic, University Hospital "Alexandrovska", 1, Sv. G. Sofiiski str., Bg - 1431 Sofia, tel. +3592 9230 528, e-mail:


Contrast-induced nephropathy - 42, 2006, No 3, 9-17.
D. Paskalev

Hospital "Sv. Marina", Medical University Varna
Summary: Contrast-induced nephropathy (CIN) is definited by the European Society of Urogenital Radiology (ESUR) as a condition in which an imprairment in renal function (an increase in serum creatinine by more than 25% or 44 µm>l/l) occurs within 3 days following the intravascular administration of contrast media (CM) in the absence of an alternative etiology. Pre-existing renal insufficiency, diabetic nephropathy, dehydration, congestive heart failure, aged, concurrent administration of nephrotoxic drugs (gentamicin, cisplatin, nonsteroidal antiinflammatory drugs etc.) and the dose and type of CM are considered to be risk factors. The reduction in the renal perfusion caused by direct effect of CM on the kidney and the toxic damage to tubular cells are the main factors in the pathogenesis of CIN. Overall, the incidence of CIN is 20-30% in the presence of risk, with approximately 2% requiring hemodialysis. Mortality among the patients requiring temporary or long-term dialysis is high (12-37%). Hydration and the use of low-osmolar or iso-osmolar CM are the most important measures against CIN. The efficacy of the other preventive means, particularly the use of dopamine, N-acetylcysteine, theophylline and calcium antagonists remains uncertain. The administration of furosemide and mannitol is no longer recommended. Nonsteroidal antiinflammatory drugs and diuretics should be withheld for at least 24 hours before and after exposure to CM, if possible. Alternative imaging techniques not requiring the administration of CM are considered in the presence of high-risk.
Key words: contrast-induced nephropathy, contrast media
Address for correspondence:
Assoc. Prof. Dobrin Paskalev, M.D., Clinic of Nephrology and Dialysis, University Hospital "Sv. Marina", 55, Marin Drinov Str., Bg - 9002 Varna, tel. +359 052 302 951, e-mail:


Current problems of the immunological diagnosis of autoimmune diseases - 42, 2006, 3, 18-20.
K. Nikolov(1) and M. Baleva(2)

(1)Clinic of Dermato-Venereology, MHAT "Sv. Anna" - Varna
(2)Department of Allergology and Asthma, University Hospital "Alexandrovska" - Sofia
Summary: Autoimmune diseases affect approximately 5% of the population and their prevalence is increasing constantly. The new approaches towards the diagnostics of autoimmune diseases include: 1. Early detection of the predisposition to autoimmune diseases. 2. Development of new techniques for detection of antibodies. The problems associated with the development of new diagnostic methods and the early diagnosis of the first symptoms of these diseases require the participation of the clinical immunologist in the diagnostic and the therapeutic process. The constantly increasing number of new autoimmune markers necessitates new multicenter studies aimed at consensus statements on the problems of autoimmune diseases and conditions.
Key words: autoimmune diseases, diagnosis
Address for correspondence:
 Prof. Marta Baleva, M. D., Department of Allergology and Asthma, University "Alexandrovska" Hospital, 1, "Sv. G. Sofiiski" Str., PO Box 45, Bg - 1431 Sofia, 5-mail:



Common features and specificity of receptors and coreceptors in infection with Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and HIV + HCV - 42, 2006, 3, 21-26.
S. Slavova(1), K. Nikolov(1), B. Grigorov(2), S. Raleva(3) and R. Argirova(3)

(1)Department of Dermatovenereology, Medical University - Varna
Laboratoire de Virologie Humaine, Ecole Normale Superieure de Lyon France
(3)Laboratory of Retroviruses, National Institute of Infectious and Parasitic Diseases Sofia
Summary: HCV is a member of the Flaviviridae family. The HCV infection is one of the most important health problems worldwide. Nearly 3% (170 million people) of human population is HCV infected. More than 70% of the infected people develop a persistent infection which could later progress to cirrhosis and/or hepatocellular c0rcinoma. Despite the efforts of a number of research groups and clinicians, the mechanisms of HCV infection are still not well understood leading to less effective therapeutic results. Though, the therapy with PegINF + Ribavirin might clear the virus in 41-54% of patients infected with HCV genotype 1a. Due to similar transmission of HIV and HCV, the co-infection with HCV is one of the most common among HIV infected individuals - nearly 30% of them are infected with both viruses. In co-infected persons, the evolution of HCV infection is more rapid and aggressive. The therapy for those patients should be individually adjusted. All this requires further investigation of HIV and HCV life cycles during the course of co-infection to achieve optimal therapeutic results. The objective of this review is to shed light on the mechanisms of attachment and receptor and co-receptor mediated entry of HCV and HIV, e.g. the joint impact of both viruses during the initiation of co-infection. Knowledge of molecular entry mechanisms might be an important tool for efficient therapy of HIV-HCV co-infection.
Key words: coinfection, HIV, HCV, CCR5, CXCR4, DC-SIGN, L-SIGN, CD81
Address for correspondence: Stanimira Slavova, M. D., Department of Dermatovenereology, Medical University, 100, Tzar Osvoboditel Str., Bg - 9000 Varna



Modern trends in antithrombotic therapy - 42, 2006, No 3, 27-31.
A. Goudev

Department of Cardiology, University Hospital "Tzaritza Ioanna" - Sofia
Summary: The modern treatment of thrombosis is one of the major challenges of medical treatment. Old generation antithrombotic drugs have unpredictable pharmacokinetics and require expensive laboratory monitoring. The new drugs like factor Xa inhibitor fondaparinux are effective and safe in a broad range of clinical implications. The major advantage of this drug is the once daily application and the reduced incidence of major bleedings.
Key words: anticoagulation, thrombosis, fondaparinux
Address for correspondence:
Assen Goudev, M. D., Department of Cardiology, Hospital "Tzaritza Ioanna", 8, Bialo more Str., Bg - 1527 Sofia, e-mail:




Antiphospholipid syndrome- 42, 2006, № 2, 5-15.
E. Vikentieva and M. Baleva

Laboratory of Clinical Immunology, Department of Allergology and Asthma, University Hospital “Alexandrovska” – Sofia
Summary:The antiphospholipid syndrome (APS) is a systemic autoimmune disorder of unknown etiology. It is characterized by arterial and/or venous thrombosis (often multiple), pregnancy morbidity (mainly recurrent fetal losses and premature birth) and mild-to-moderate thrombocytopenia in patients with laboratory evidence for presence of antiphospholipid antibodies. The most important types of antiphospholipid antibodies in APS are lupus anticoagulant, anticardiolipin antibodies and recently anti-beta2GPI antibodies. Other autoantibodies, which are frequently detected in many patients with APS, are antimitochondrial, antiendothelial cell, antiplatelet, antierythrocyte and antinuclear antibodies. The APS in patients having neither clinical nor laboratory evidence of another disease is defined primary APS. The APS associated with another autoimmune disease is named secondary APS (most commonly SLE).
Key words: antiphospholipid syndrome, antiphospholipid antibodies, lupus anticoagulant, SLE, thrombophilia
Address for correspondence: Elena Vikentieva, M.D., Laboratory of Clinical Immunology, Department of Allergology and Asthma, University Hospital Alexandrovska, 1, Sv. G. Sofiiski Str., Bg – 1431 Sofia, e-mail:



Malignant melanoma: diagnosis and prognosis - 42, 2006, № 2, 16-22.
F. Georgieva and Kr. Nikolov

Department of Dermatology and Venerеology, Hospital Sv. Anna - Varna
Summary: Melanoma is a malignancy of pigment-producing cells occurring in the skin, eyes, ears, gastrointestinal tract, leptomeninges of the central nervous system, and oral and genital mucous membranes. Melanoma accounts for only 4% of all skin cancers; however, it causes the greatest number of skin cancer-related deaths worldwide. Early detection of thin cutaneous melanoma is the best means of reducing mortality. The article presents epidemiology, clinical types, diagnostic approach and algorithm of conduct in patients with cutaneous malignant melanoma. Analysis of possibilities of different diagnostic approaches and prognostic scales is made.
Key words: malignant melanoma, clinical types, diagnosis, prognosis
Address for correspondence:
F. Georgieva, M. D., Clinic of Dermatology and Venereology, Hospital "Sv. Anna", 100, Tzar Osvoboditel blv., Bg – 9000 Varna



Ambulatory therapy of chronic heart failure - 42, 2006, № 2, 23-29.
A. Doychinov and S. Machev

National Cardiology Hospital - Sofia
Summary: Modern therapeutic means make the prognosis of heart failure much better, but the achieved success is still not enough. During the last two decades, the 5-year cardiovascular mortality in patients with heart failure lowered down in men from 70% to 59% and in women from 57% to 45%. The Euro Heart Failure Survey (EHFS) program gives data, that the therapeutic possibilities available are still not optimal used. This fact concerns mostly the therapy with ACE-inhibitors, angiotensin-receptor blockers and beta-blockers. All large multicenter studies established the favorable effect of these drugs in lowering down the cardiovascular mortality in cases of heart failure, so they are certain part of the basis therapy in this illness. It is necessary more frequent to use them under strict medical control, in correct dosage and taking account of individual factors and concomitant diseases as well.
Key words: heart failure, therapy, ACE-inhibitors, beta-blockers
Address for correspondence:
Stefan Machev, M. D., National Cardiology Hospital, 65, Konjovitza Str., Bg 1309 Sofia, GSM + 359 886 57 51 64



The stem cells - 42, 2006, № 2, 30-34.
G. Milchev

IMB – Bulgarian Academy of Sciences – Sofia
Summary: Stem cells are engaged in constant crosstalk with their environment. The biochemical signalling going on between adult stem cells and their support cells often involves the same molecular pathways that direct tissue generation during embryonic developmentsuch as the Wnt, Notch and TGF-beta. To find the optimal conditions for stimulating stem cells therapeutically, biologists will need to know how stem cells and their neighbours depend on one another for survival. Difficulties in working with stem and progenitor cells in vitro arise from their propensity to differentiate. Key methodologies that have sought to overcome such limitations include transgenic/knock-out animals and in vitro studies using murine embryonic stem cells. The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets. Strategies for regenerating CNS and cardiac tissues with tissue-specific cells rely on the pluripotency of bone marrow and umbilical cord blood stem cells. Mutations resulting in wrong signals as well as replacement of stem cells in the wrong tissue in the body might conceivably form a malignant tumor. Embryonic stem cells don't live in such complex microenvironments as their adult counterparts. They have the potential to give rise to all of the body's tissues. The low efficiency of directed differentiation of human embryonic stem (hES) cells remains a major obstacle in their uses for regenerative medicine. The recent availability of hES cells suggests that a system for stable and efficient manipulations of hES cells without loss of their pluripotency is now at hand.
Key words: stem cells, differentiation, mutations, regenerative medicine
Address for correspondence:
Georgi Milchev, M. D., 54, Skobelev Blvd., Bg – 1606 Sofia, tel. + 359 2 953 0983


CRP – a new and promising marker for identification of coronary heart disease - 42, 2006, № 2, 35-39.
P. Jordanova-Laleva(1) and N. Petrova(2)

(1)Clinical Laboratory, University Hospital G. Stranski” – Pleven
(2)Clinic of Endocrinology, University Hospital G. Stranski” – Pleven
Summary:Coronary heart disease (CHD) remains the leading cause of morbidity and mortality in industrialized world. Atherosclerosis, the underlying cause of most CHD is a process that involves multiple elements, with chronic inflammation playing a significant role. Measuring low concentrations of acute phase reactants like C-reactive protein (CRP) may provide a new method for identification of individuals at increased risk for CHD. Several large prospective studies demonstrated that CRP is a predictor of future coronary events in apparently healthy individuals. The simultaneous measurement of CRP and serum lipids may improve the prediction of global coronary risk at individuals who have either increased or normal serum cholesterol concentrations. The heightened interest in reliable measurement of low CRP concentrations provoke development of high-sensitivity CRP (hs-CRP) methods as a tool for the primary prevention of CHD. Preventive therapies to attenuate coronary risk in individuals with increased hs-CRP include aspirin and statin-type drugs.
Key words: сoronary heart disease, inflammation, prevention
Address for correspondence:
Natalia Petrova, M. D., Clinic of Endocrinology, UMHAT, 8, Georgi Kochev Str., Bg - 5800 Pleven, tel. +359 64/886-642,



Development and growth of cranio-facial complex - 42, 2006, № 2, 40-43.
A. Djorov(1) and I. Djorova(2)

(1)Department of Oral and Maxillofacial Surgery, Faculty of Stomatology, Medical University – Sofia
(2)Medico-Dental Center “AMA”  Sofia
Summary: There are presented the embryogenesis of lower and upper jaw and their relation to the other facial and cranial structures as well as their postnatal development. Etiology, pathogenesis and time for surgical reconstructions of dento-maxillo-facial anomalies and deformations are related to development and growth of the cranio-facial complex.
Key words: development, growth, cranio-facial complex
Address for correspondence:
 Anton Djorov, D. D. , OMFS, Faculty of Stomatology, MU, 1, Sv. G. Sofijski Str., Bg 1431 Sofia, tel. +359 888 77 82 84, e-mail:



Modern methods for detection of biological warfare agents - 42, 2006, № 2, 44-52.
I. N. Ivanov

National Centre of Communicable and Parasitic Diseases - Sofia
Summary: The problem of timely detection of biological warfare agents has become a global priority. An increasing number of publications reveal a variety of novel detection methods, most of which in the field of molecular genetics. The great advancement in the DNA amplification and hybridization techniques and their automation made the detection of important pathogens possible within a few hours. The rapid identification of causative agents is crucial for undertaking important decisions and adequate measures for protecting people. The current review presents the contemporary molecular methods based on DNA technology, DNA amplification and hybridization methods and their application for detecting biological agents. There are also considered the general trends for their development and optimization.
Key words: detection, biological agents, DNA amplification and hybridization, polymerase chain reaction, DNA chips
Address for correspondence:
Ivan N. Ivanov, National Centre for Condagious and Parasitic Diseases, 26 Yanko Sakazov Blvd., Bg 1504 Sofia, tel. +359 2 944 6999/ext. 290, 353, e-mail:



Supplement 2

Ml. Grigorov, M. Tsekova and Y. Usunangelov. Acute coronary syndrome. Manual. Ed. Ml. Grigorov. MU Sofia, CML, 2006. 48 p.



Diabetes mellitus in patients with kidney transplantation - 42, 2006, № 1, 5-11.
E. Paskalev
Clinic of Nephrology and Transplantation,
University Hospital "Alexandrovska" – Sofia
Summary: Kidney transplantation is a main treatment of chronic renal failure. In recent years, diabetes mellitus after kidney transplantation has been identified as a major risk factor to both graft and patient survival. There are two main clinical problems – pre-existing diabetes mellitus and new-onset
(post-transplantation) diabetes mellitus. Patients with pre-existing diabetes mellitus need much more control, especially if they are treated with immunosuppressive agents that impair glucose metabolism. Transplantation may accelerate the development of diabetes mellitus – new-onset diabetes mellitus. There are many risk factors – family history of diabetes, glucose intolerance, obesity, age, immunosuppressive therapy, HLA phenotype, hepatitis C virus infection, ethnic background. Estimates of the incidence of this diabetes vary from 1.8% to 53.6%. The importance of post-transplantation diabetes mellitus is great as diabetes decreases survival rate of both graft and patient.
Key words:  diabetes mellitus, diabetic nephropathy, kidney transplantation
Address for correspondence:
 Assoc. Prof. Emil Paskalev, M. D., Clinic of Nephrology and Transplantation, University Hospital “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg 1431 Sofia, tel. +359 2 923-02-40, e-mail:



Rheumatoid arthritis and chronic parodontitis – chronic diseases with common pathogenesis - 42, 2006, № 1, 12-18.
M. Panchovska
(1) and E. Firkova(2)
(1)Department of Propedeutics of Internal Diseases, MF, MU – Plovdiv
(2)Department of Parodontology and Oral Mucose Diseases, DF, MU – Plovdiv
Summary:  Rheumatoid arthritis (RA) is a chronic inflammatory progressive disease. It provokes invalidization in part of patients. 0,5-1 per cent of the population suffers from RA. It is characterized by early development of bone erosions – 2 years after start of the disease 75 per cent of patients have roentgenographic changes. The etiology of RA is unknown and etiotropic treatment is impossible. The area of interest are the common pathogenesis and possible relation between RA and chronic parodontitis (CP). The results of different investigations established such a relation. 3,95 per cent from patients with CP suffer from RA vs 1 per cent frequency of RA in the common population. There are no investigations on severity of RA in correlation with severity of CP. In this review, the common positions and the differences between RA and CP were discussed. The processes of chronic inflammation are immunogenetic dependent. In this sense, we may use similar or identical medicaments for immune response modulation and for inhibition of immune type of inflammation.
Key words: rheumatoid arthritis, chronic parodontitis, pathogenesis, immune response
Address for correspondence
Assoc. Prof. Maria Panchovska, M.D., Clinic of Rheumatology, Medical University, 15A, V. Aprilov Blvd., Bg - 4000 Plovdiv, tel.  +359 32 60-23-61



Psoriatic arthritis diagnosis, pathogenesis and therapy - 42, 2006, № 1, 19-28.
G. Тсhernev and D. Trebing
Department of Dermatology and Immunology, Municipal Hospital  Dessau, Germany
Academic Educational Hospital of Martin Luther University  Halle-Wittenberg, Germany
: Psoriatic arthritis (PsA) is an inflammatory type of arthritis that shares some features with rheumatoid arthritis, but may be distinguished by unique clinical manifestations, characteristic radiographic findings and the absence of rheumatoid factor. PsA can begin in any age group. On overage, it appears about 10 years after the first signs of psoriasis. In most patients, it manifests from the age of 30-50 years. In about one of 7 people with PsA, arthritis symptoms occur before any skin lesions appear. Rarely, patients might have PsA without psoriasis. The cellular events underlying the pathogenesis of psoriatic arthritis and psoriasis have not been yet elucidated. In particular, a growing body of data supports the role of proinflammatory cytokines such as TNF-alpha in the pathophysiology in PsA and psoriasis. Raised level of this cytokines are found in the joints of patients with PsA, as well as in psoriatic skin lesions. Physiotherapy, non steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease modifying antirheumatic agents (DMARDs), such as methotrexate, are the most commonly used treatments for PsA. Newer agents such as TNF-alpha inhibitors target inflammatory cytokines, chemocytokines and T-cells and may be particularly effective for patients who fail DMARD or have inadequate response to NSAIDs. Infliximab, a TNF-alpha inhibitor, has been shown to be effective in patients with psoriatic arthritis. Etanercept treatment is also well tolerated and resulted in significant improvement in the signs and symptoms of psoriatic arthritis and in psoriatic skin lesions.
Key words:  psoriatic arthritis, diagnosis, therapy
Address for correspondence: 
Georgi Tchernev, M. D., Department of Dermatology and Immunology, Municipal Hospital, Auenweg 38, 06847 Dessau, tel.  0049 340 501 4050/4056, GSM 0049 1622643815, e-mail:



Hypertensive retinopathy – means of stratification of the heart and cerebral vascular risk in hypertensive patients - 42, 2006, № 1, 29-33.
I. Shterev, J. Georgieva and K. Nenova
Department of Internal Medicine, Medical Univercity – Varna, MHAT ''Sv. Marina'' Varna
Summary: Many clinical trials and issues of the American National Committee on prevention, early diagnosis and treatment of arterial hypertension (JNC), point retinopathy as a marker of affection of the target organs by AH. Despite the recommendations of GNC, the clinical criteria of hypertensive retinopathy (HR) are still uncertain, no firm consensus, regarding its classification and role as a risk stratification possibility, exists. Although a lot of trials determine higher mortality in patients with HR, few of them establish a definite relationship between HR and the risk of development of specific vascular incidents as brain stroke and acute or chronic ischemic heart disease. This is due to lack of objective ophthalmoscopic criteria about HR, on the one hand, and to the fact that the involved patients were untreated or poorly treated, on the other. These statements impose the initiation of a more informative and sensitive diagnostic method of confirming the HR in clinical practice by standard photos of the fundus. The purpose of this survey is to revise the trials since 1990, related to pathophysiology, epidemiology and the possibility to apply HR for stratification of risk in patients with AH.
Key words: hypertensive retinopathy (HR), arterial hypertension (AH), ischemic heart disease (IHD), cerebral vascular disease (CVD)
Address for correspondence:
Ivan Shterev, M. D., Department of Internal medicine, MHAT ''Sv. Marina'', 1, Hristo Smirnenski Str., Bg – 9000 Varna, e-mail:



Neurotrophins and apoptosis - 42, 2006, № 1, 34-39.
D. Prodanov
(1, 2),  G. Manchev   and N. Boiadzhieva(1)
(1)Department of Pharmacology and Toxicology, Medical Faculty - Sofia
(2)Neuroregulation group, Department of Neurosurgery, Leiden University Medical Center
Summary: Neurotrophins are important factors for the neuronal cell survival. This review is focused on the effects of neurotrophins in the nervous system and their interaction with apoptosis. Mechanisms of apoptosis are concisely described with emphasis on the caspase enzymatic system. The interplay between the apoptotic pathway and the signal pathways of neurotrophin receptors – trk A, B, C and p75, is discussed. Understanding of the mechanisms of action of neurotrophins increases our knowledge on apoptosis and its interaction with other cell functions such as mitosis and differentiation. It may prove instrumental for the treatment of neurodegenerative disorders, nerve injuries and tumors.
Key words: neurotrophins, functions, mechanisms of action, apoptosis
Address for correspondence: 
Dimiter Prodanov, M. D., Neuroregulation group,
Leiden University Medical Center, PO Box 9604, 2300 RC Leiden, Netherlands, e-mail:



Genetic mechanisms of leukemogenesis - 42, 2006, № 1, 40-43.
M. Velizarova
(1) and I. Dimova(2)
(1)Chair of Clinical Laboratory and Clinical Immunology, Medical University – Sofia
(2)Chair of Medical Genetics, Medical University – Sofia
Summary:  The genes, which participate in the carcinogenesis, are divided into two main groups: oncogenes and tumor suppressor genes (TSG). The protooncogenes are normal cell genes that have positive control on the cell proliferation and differentiation. When their structure and function are injured as a result of chromosomal translocations, inversions, point mutations and gene amplifications, they have a power to induce tumor growth. TSGs are negative regulators of cell functions, which affect mainly the expression of oncogenes. Normal cells transform into malignant cells after TSG inactivation as a result of mutations or deletions in the respective chromosomal regions. Detection of genetic changes of leukemic cells has exceptional role for more complete investigation of the reasons and proceeding of malignant blood diseases, for patients’ prognosis as well as for the development of target molecular therapy.
Key words:  leukemogenesis, oncogenesis, molecular basis of leukemia
Address for correspondence:
 M. Velizarova, M. D. Chair of Clinical Laboratory and Clinical Immunology, 1, Sv. G. Sofijski Str., Bg – 1431 Sofia, tel. +359 2 91-72-401, e-mail: m_velizarova



Oxidative stress, gastric ulcer and protection by N-acetylcysteine - 42, 2006, № 1, 44-47.
G. Bekyarova
(1), B. Galunska(2) and T. Yankova(2)
(1)Department of Pathophysiology,
(2)Department of Biochemistry
Medical University Varna
Summary: Oxidative stress and associated with it processes of lipid peroxidation are important factors in ulcerogenesis induced by chemical agents, such as ethanol, acetylsalicylic acid, indomethacin. The activation of lipid peroxidation decreases endogenous antioxidantsmucosal glutathione, glutathione peroxidase etc. N
-acetylcysteine (NAС) as a donor of a substrat (Cystein) for reduced glutathione biosynthesis and as an antioxidant (”scavenger” of H2O2, HOCL), has a protective effect on the indomethacin induced gastric oxidative injury .
Key words: N-acetylcysteine, ulcerogenesis, glutathione, oxidative stress
Address for correspondence:
Assoc. prof. Ganka Bekiarova, M. D., Department of Pathophysiology, Medical University, 55, Marin Drinov Str., Bg – 9002 Varna, tel. +359 52-670-035, е-mail:



Maxillary and bimaxillary reconstructions in the orthognatic surgery - 42, 2006, № 1, 48-52.
A. Djorov

Department of Oral and Maxillofacial Surgery, Faculty of Stomatology, Medical University – Sofia
Summary: The maxillary deformations can be isolated but more often they are related to anomalies of other parts of the cranio-facial complex or they are a part of syndromes. Their surgical treatment is by segmental maxillary osteotomies, total maxillary or bimaxillary orthognatic reconstructions. We present the used surgical methods. On the base of the literature data and our own surgical experience, we give the basic indications of their use. We present in detail the segmental maxillary osteotomies and total reconstructions of the upper jaw (Le Fort I type). We give also information about the bimaxillary reconstructions and corrections of the middle third of the face.
Key words:   maxillary reconstructions, osteotomies, Le Fort I, bimaxillary reconstructions, distraction osteogenesis
Address for correspondence:
 Anton Djorov, M.D., Department of Oral and Maxillofacial surgery, Faculty of Stomatology, Medical University, 1, Sv. G. Sofiiski Str., Bg – 1431 Sofia, e-mail:, tel. +359 2 962-55-79, +359 2 868-43-65


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