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Vol. 46, 2010


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4'2010

The need for quantitative indicators in studying prevalence, evolution and treatment of diabetes mellitus - 46, 2010, № 4, 5-11.
V. Valov(1) and M. Boyanov(2)
(1)Novo Nordisk Pharma EAD, (2)Endocrinology Clinic -- University Alexandrovska Hospital, Department of Internal Medicine, Medical University -- Sofia
Summary: Diabetes mellitus is becoming an epidemic of greatest impact. The absolute number of diabetic patients is expected to grow by 50% for less than 20 years. The prevalence of diabetes mellitus in Bulgaria is around 8,3% of the adult population over 20 years. The trend for late diabetes diagnosis is leading to increasing direct and indirect costs with hospitalizations accounting for more than half of all costs. For planning purposes, a diabetes registry is needed with all medical procedures and activities being included. There is a growing need for implementation of objective indicators for diabetes management quality. Small increments in the diabetes treatment cost today are an investment with great potential for substantial savings in future.
Key words: diabetes mellitus, insulin analogs, pharmacoeconomics, cost-effectiveness
Address for correspondence: Assoc. Prof. Mihail Boyanov, Endocrinology Clinic -- University Hospital „Alexandrovska”, 1, G. Sofiiski Str., Bg -- 1431 Sofia, tel. +359 2 9230 784, e-mail: boyanov@alexandrovska-hospital.bg

 

 

What is the cost of diabetes mellitus? - 46, 2010, № 4, 12-17.
M. Boyanov(1) and V. Valov(2)
(1)Endocrinology Clinic -- University Hospital „Alexandrovska”, Department of Internal Medicine, Medical University -- Sofia, (2)Novo Nordisk Pharma EAD
Summary: Diabetes mellitus is a chronic disease, leading to a broad spectrum of complications. In the last decade, a lot of data have accumulated favoring the early diagnosis and aggressive treatment of diabetes type 2 as an investment in reducing future financial and human costs of diabetic complications. Hospitalizations consume more than half of all funds, whereas oral and insulin treatment -- only 7-10% of the direct costs. The cost of diabetes is therefore produced mainly by the complications and complications at the other hand -- by poor glycemic and metabolic control. The active and complex management of diabetes can lead to increased life expectancy -- by several years free of complications. Increasing the costs of treatment today may lead to considerable savings in the future. The early investment in the diagnosis and treatment of diabetes may lead to great advantages in the long term.
Key words: diabetes mellitus, pharmacoeconomics, costs, investment strategy
Address for correspondence: Assoc. Prof. Mihail Boyanov, Endocrinology Clinic, University Hospital „Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg -- 1431 Sofia, tel. +359 2 9230 784, e-mail: boyanov@alexandrovska-hospital.bg

 

 

Pathogenetic mechanisms of the hypertension induced by inhibitors of VEGF - 46, 2010, № 4, 18-23.
G. Krasteva(1) and E. Lakova(2)
(1)Division of Experimental and Clinical Pharmacology, (2)Division of Pathophysiology, Medical University – Pleven
Summary: Angiogenesis is а critical factor for the growth and metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) plays a central role in the pathological angiogenesis. Inhibition of angiogenesis with monoclonal antibodies to VEGF (bevacizumab) or with tyrosine kinase inhibitors targeting VEGF receptors (sorafenib, sunitinib) has become an established treatment for various cancers. Contrary to expectation, a number of adverse effects (hypertension, proteinuria, hemorrhage and thrombosis, gastrointestinal perforation, impaired wound healing) have been reported. Although hypertension appears to be one of the most common adverse effects of VEGF inhibitors, the pathophysiological mechanisms underlying the increase in blood pressure are not fully understood. Several hypotheses regarding the origin of hypertension have been postulated: decrease in the production of endothelium-derived relaxing factors (NO, PGI2) and/or enhanced production of vasoconstricting factors (TxA2, ET-1), reduction of the renal hemodynamics, microvascular rarefaction, increase in arterial stiffness, inhibition of VEGF-C signaling, thyroid dysfunction.
Key words: angiogenesis, cancer, hypertension, vascular endothelial growth factor
Address for correspondence: Genka Krasteva, M.D., Division of Experimental and Clinical Pharmacology, Medical University, 1 Kl. Ohridski Str., Bg --5800 Pleven, +359 64 884 282, e-mail: krusteva_med@abv.bg

 

 

Vitamin D: beyond the calcemic effect - 46, 2010, № 4, 24-33.
D. Gerova(1), B. Galunska(2) and D. Paskalev(3)
(1)Section of Clinical Laboratory, (2)Department of Biochemistry, Molecular Medicine and Nutrigenomics, (3)Section of Nephrology and Dialysis, Medical University --Varna
Summary: It is defined that vitamin D deficiency is related to numerous chronic diseases such as chronic kidney disease, diabetes, cardiovascular diseases, cancer, multiple sclerosis, and cognitive diseases. A relationship between vitamin D deficiency and development of hypertonia, myocardial infarction, dyslipidemia, and increased prone to thrombosis is established. The antiproliferative effect of 1,25-(ОН)2 D3 (calcitriol) on mouse and human leukemic cells, and on human keratinocytes encourages numerous surveys on the clinical efficacy of 1,25-(ОН)2 D3 and its analogues in the treatment of leukemias and psoriasis. Uncovering the molecular mechanisms of vitamin D action is the basis of new drug development with minimal unwanted effects. Plasma levels of 25-ОН D3 are accepted as a biomarker for evaluation of vitamin D status. Plasma levels above 75 nM are sufficient for optimal health and cancer prevention.
Key words: vitamin D deficiency, cardiovascular diseases, cancer, chronic kidney disease
Address for correspondence: Daniela Gerova, Section of Clinical Laboratory, Medical University --Varna

 

 

Molecular methods in the diagnostics of anaerobic infections - 46, 2010, № 4, 34-41.
V. Tolchkov, M. Marina and K. Kantardziev
Division of Microbiology, National Centrе of Infectious and Parasitic Diseases -- Sofia
Summary: The development of molecular methods in the last two decades and their more conventional application both in scientific research and in clinical practice support the fast diagnostics and typing of pathogenic anaerobic bacteria. The classical microbiological methods have much lower discrimination and need up to one week cultivation time which might be critical for the correct diagnosis and the treatment of the patient. In this review, there are listed the main modern molecular methods and their application for diagnostics and typing of the causative agents of anaerobic infections.
Key words: anaerobic infections, molecular methods, diagnostics, typing, Clostridium difficile
Address for correspondence: V. Tolchkov, Division of Microbiology, NCIPD, 26, Ianko Sakazov str., tel. +359 878195518, е-mail: tolchkov@gmail.com

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3'2010

Biochemical markers evaluating bone metabolism – 46, 2010, № 3,  5-16.
D. Gerova and B. Galunska.
(1)Department of General Medicine and Clinical Laboratory, Section of Clinical Laboratory, Medical University -- Varna, (2)Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University -- Varna
Summary: Various biochemical markers can be used for evaluation of both bone resorption and bone formation -- major processes in bone remodeling. Widely used markers of bone turnover are bone alkaline phosphatase, osteocalcin, procollagen propeptides, hydroxyproline, tartrate-resistаnt acid phosphatase, pyridinoline crosslinks, collagen telopeptides, cathepsin K, vitamin D and its metabolites. Recently, a growing amount of data related to the molecular mechanisms of bone metabolism revealed new markers of bone turnover: proteins regulating osteoblasts’ and osteoclasts’ activation like the receptor activator of nuclear factor-kB (RANK) and its ligand (RANKL), and the natural inhibitor of the ligand -- the cytokine osteoprotegerin (OPG). Lately, the novel role of homocysteine -- an independent marker of impaired bone turnover, especially in osteoporosis, and its relation to the fracture risk are studied.
Key words: biochemical markers, bone turnover
Address for correspondence: Daniela Gerova, M. D., Department of General Medicine and Clinical Laboratory, Section of Clinical Laboratory, Medical University, 1, Christo Smirnenski Str., Bg -- 9010 Varna, e-mail: dgerova@gmail.com

 

 

Diagnostic parameters for evaluation of antiphospholipid syndrome – 46, 2010, № 3, 17-21.
M. Baleva and Kr. Nikolov.

(1)Department of Clinical Immunology, University Hospital Alexandrovska, Chair of Clinical Laboratory and Clinical Immunology, Medical University -- Sofia, (2)Department of Dermatovenereology, Chair of Dermatovenereology, Hospital “Sv. Anna”, Medical University -- Varna
Summary: Тhe main diagnostic problems of the antiphospholipid syndrome have been discussed. The significance of the determination of antibodies to different phospholipids has been analysed. The role of antibodies not only to cardiolipin and beta-2-glycoprotein I, but to prothrombin, phosphatidylserin, phosphatidylethanolamin, annexin V, etc. in antiphospholipid syndrome has been evaluated.
Key words: antiphospholipid syndrome
Address for correspondence: Prof. Marta Baleva, M. D., Department of Clinical Immunology, University Hospital Alexandrovska, 1, G. Sofiiski Str., Bg -- 1431 Sofia, e-mail: marta_baleva@yahoo.com

 

 

Drug interactions with alcohol and tobacco smoking - 46, 2010, № 3, 22-27.
S. Valcheva-Kuzmanova.
Department of Preclinical and Clinical Pharmacology and Toxicology, Medical University -- Varna
Summary: Drug interactions with alcohol and tobacco smoke are of great significance because of the high incidence of alcohol consumption and smoking among the population. These interactions may have serious consequences such as treatment failure, adverse drug reactions, toxicity. The review provides an overview of the literature on clinically important interactions of drugs with alcohol and tobacco smoke as well as the possible mechanisms for their implementation. Pharmacokinetic interactions are mainly at the level of drug and alcohol metabolism while pharmacodynamic interactions are at the level of actions and effects. Knowing the possible interactions of drugs with alcohol and tobacco smoking can help the clinician in pursuing a rational drug therapy, while avoiding the risk of dangerous adverse drug effects.
Key words: drugs, alcohol, tobacco smoking, interactions
Address for correspondence:
Assoc. Рrof. Stefka Valcheva-Kuzmanova, MD, PhD, Department of Preclinical and Clinical Pharmacology and Toxicology, Medical University, 55 Marin Drinov Str., 9002 Varna, tel. +359 52 677 078, e-mail: stefkavk@yahoo.com

 

 

Implementation of acupuncture for treatment of non-specific chronic low back pain: oriental philosophy or evidence-based practice? ? – 46, 2010, № 3, 28–33.
D. Tonev and S. Radeva.
(1)Department of Anesthesiology and Intensive Care, National Transport Hospital “Tsar Boris III” -- Sofia, (2)Department of Physiotherapy, University Hospital “Tsaritsa Ioanna -- ISUL” -- Sofia
Summary: Classical acupuncture is based on philosophical belief in the existence of meridians along the body with specific acupunctural biologically active points located on them, which after piercing the skin with fine needles are stimulated and in that way they restore the vital energy flow (“qi”) along the meridians and the balance between opposing negative and positive (“yin” and “yang”) life forces as well and cause health improvement. Recent data from meta-analyses of randomized sham-placebo and non-treatment controlled clinical trials fail to verify the traditional theory about specific mechanism of action of true/verum acupuncture and show small to moderate acupuncture analgesic effect sizes in relieving non-specific chronic low back pain. Until inert controls are found to assess the effectiveness of true/verum acupuncture, there is a consensus for the conduction of pragmatic (reflecting real clinical practice) trials comparing the true/verum acupuncture with other conventional alternative forms of non-pharmacological treatment of non-specific chronic low back pain.
Key words: true/verum acupuncture, sham acupuncture, non-specific chronic low back pain, analgesic effect
Address for correspondence:
Dimitar Tonev, M.D., Ph.D., Department of Anesthesiology and Intensive Care, National Transport Hospital “Tsar Boris III”, 108, Maria-Luisa Blvd., Bg -- 1233 Sofia, tel. +359 2 932 36 86, e-mail: dtonev61@hotmail.com

 

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2'2010

Current role of endoscopic retrograde cholangiopancreatography in diagnostic and therapeutic algorithm for diseases of pancreas and congenital pancreatobiliary malformations - 46, 2010, No 2, 5-10. 
P. Getsov(1), S. Dineva(2), B. Vladimirov(3) and P. Rusev(1)

(1)Department of Diagnostic Imaging at University Hospital "Tsaritsa Ioanna” -- Sofia, (2)Department of Diagnostic Imaging at Medical Institute of Ministry of Inferior -- Sofia, (3)Clinical Center of Gastroenterology, University Hospital " Tsaritsa Ioanna” -- Sofia
b Imaging methods play a key role in the diagnosis of pancreatic diseases. For decades, endoscopic retrograde cholangiopancreatography (ERCP) was the first choice, both in diagnostic and therapeutic plan. Technological advances that have made other imaging methods in the last decade changed this position and place of the methodology was subject to revision. Because of its invasive nature and possible complications, it is displayced by non-invasive and more sensitive imaging methods. This puts new challenges and responsibilities to specialists in diagnostic imaging, as their role in early diagnosis and surgery planning increases. Capabilities of ultrasound, CT and MRI allow to use them as a kind of screening to identify patients suitable for interventional (percutaneous and endoscopic) or surgical treatment. For the majority of diseases in the pancreas, ERCP is the primary therapeutic intervention, whose specific purpose is determined by the nature and stage of disease.
Key words: endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreatography, computed tomography
Address of correspondence: Plamen Getsov, M. D., Department of Diagnosting Imaging, Queen Joanna Hospital, 8 Bialo more Str., Bg -- 1527 Sofia, e-mail: plamegecov@abv.bg

 

 

Non-alcoholic fatty liver disease -- epidemiology and pathogenesis - 46, 2010, No 2,  11-15.
M. Boyanov and V. Grozeva
Endocrinology Clinic, Alexandrovska University Hospital, Department of Internal Medicine, Medical University -- Sofia
Summary: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver injury, characterized by macrovascular steatosis in the absence of alcohol abuse and other causes for liver disease. The liver injury may vary from pure steatosis, steatohepatitis to fibrosis, cirrhosis and clinically overt liver failure. There is a reciprocal link between insulin resistance and the liver injury. Today NAFLD is seen as a liver manifestation of the metabolic syndrome. NAFLD has an epidemic prevalence and is an independent risk factor for acute coronary and brain incidents as well as for malignant neoplasms.
Key words: non-alcoholic fatty liver disease, insulin resistance, obesity, cardiovascular risk
Address for correspondence: Assoc. prof. Mihail Boyanov, M. D., Endocrinology Clinic, Alexandrovska University Hospital, 1, Sv. G. Sofiiski Str., Bg -- 1431 Sofia, tel. +359 888 971 203, e-mail: boyanov@alexandrovska-hospital.bg

 

 

On possible participation of human polyomavirus JC in the colorectal cancer oncogenesis - 46, 2010, No 2, 16-22.
Z. Kalvachev(1), I. Tsekov(1), D. Stoyanova(2), D. Dardanov(3), K. Katsarov(2), G. Kirov(3) and S. Hristova(2)
(1)Molecular Virology Laboratory, National Center of Infectious and Parasitic Diseases, (2)Clinic of Gastroenterology, Military Medical Academy, (3)Department of Surgery, Medical Institute -- Ministry of Interior, (4)Central Cytopathology Laboratory, University Hospital „Alexandrovska”
Summary: Infections with human polyomavirus JC (JCV) are ubiquitous and lifelong. Recent data suggest that JCV may be etiopathogenetically linked to colorectal cancer, directly and/or indirectly affecting various stages of the oncogenesis. Thus, the chronic JCV infection might be an alternative to the "genetic predisposition" in this type of cancer. At least two virus-specific proteins -- the large tumor antigen (T-Ag) and so called agnoprotein, influence the control of cell cycle and induce genomic instability, creating conditions for cell transformation. Parts of viral DNA are found in cancerous tissue, which suggests that viral integration may also cause chromosomal damage. Furthermore, inflammatory infiltration in chronic irritation contributes to the accumulation of cytokines in the affected intestinal area, which may further influence the course of oncogenesis. This review discusses the hypothesis that JCV participates as a relevant factor in the genesis of colon cancer.
Key words: human polyomavirus JC, colorectal cancer
Address for correspondence: Prof. Zlatko Kalvatchev, M.D, Ph.D., Laboratory of Molecular Virology, National Center of Infectious and Parasitic Diseases, 44-A Stoletov Blvd., Bg -- 1233 Sofia, Bulgaria, tel. +359 2 931-07-13 ext. 232, e-mail: kalvatchev@gmail.com

 

 

Intracellular signaling pathways taking part in the gene expression of proinflammatory cytokines - 46, 2010, No 2,  23-26.
Tzv. Markova
Department of Pharmacology and Toxicology, Medical University -- Sofia
Summary: This clinical review focuses on some intracellular interactions and mechanisms leading to lymphocyte activation. MAPK are serine-threonine protein kinases which play an important role in transport of extracellular signals to the nucleus and regulation of expression of genes taking part in proliferation, differentiation and apoptosis. Recently, the attention has been focused on the role of ERK MAPK in the regulation of cell cytokine secretion. In T lymphocytes, ERK2 is a predominant form of MAPK. One of the most investigated functions of MAPK signaling pathways is the regulation of gene expression as a result of extracellular stimuli. cAMP/PKA is another signaling cascade taking part in the gene expression of inflammatory cytokines. cAMP and cGMP are important second messengers which play a key role in the regulation of cell activity. There is no signaling pathway in the cell which acts without influence of other signaling cascades. There is a “cross-talk” between different signaling cascades in the cell. Study of intracellular interactions and mechanisms of inflammatory cytokine gene expression would enable to realize control on these processes and their pharmacological influence.
Key words: MAPK, cAM/PKA, T lymphocytes, IL-4, IL-5
Address for correspondence: Tzvetanka Markova, M. D., Department of Pharmacology and Toxicology, Medical University, Bg -- 1431 Sofia, e-mail: tzvetanka.markova@gmail.com

 

 

Food and drug interactions - 46, 2010, No 2,  27-30.
S. Valcheva-Kuzmanova
Department of Preclinical and Clinical Pharmacology and Toxicology, Medical University -- Varna
Summary: Food as a whole as well as components of the meal can interact with drugs and thus alter drug pharmacokinetics and pharmacodynamics. Food and drug interactions can lead to serious consequences such as treatment failure and adverse drug reactions. The effect of food as a whole determines the considerations for applying certain drugs before, during or after meals. The influence of meal components on drugs necessitates taking into account the possible consequences of the concomitant intake of drugs and certain foods.
Key words: food, drugs, interactions
Address for correspondence: Assoc. рrof. Stefka Valcheva-Kuzmanova, MD, PhD, Department of Preclinical and Clinical Pharmacology and Toxicology, Medical University, 55 Marin Drinov Str., 9002 Varna, tel. 052/ 677 078, e-mail: stefkavk@yahoo.com

 

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1'2010

Genetic polymorphisms of glutathione S-transferases in human population and association with multifactorial diseases. Part II - 46, 2010, No 1,  5-13.
I. Andonova(1, 2) and V. Ganev(3)

(1)Institute of Experimental Pathology and Parasitology, BAS -- Sofia, (2)Department of Medical Chemistry and Biochemistry, Medical University -- Sofia, (3)Medical Faculty -- Sofia, Sofia University „Sv. Kl. Ohridski”
Summary: Associations between GST variants and various multifactorial diseases, most of them malignant, have been described. There are published data about associations of the polymorphic variants of the GSTs, alone or in combination, or in interactions with other factors, such as xenobiotic metabolizing enzymes, epidemiological or clinical factors, with many multifactorial diseases. Selected part of association studies published in the last decade are summarized here. The results of association of GSTs with carcinomas of mammary gland, digestive, pulmonary and other organs and systems are quite controversial. The intriguing data presented about associations of the GSTs polymorphisms with cancer diseases only confirm the complexicity of the processes involved in the chemical and endogenously induced carcinogenesis and the role of the numerous detoxification gene products of the xenobiotic metabolizing enzymes.
Key words: genetic polymorphisms, glutathione S-transferases, multifactorial diseases
Address for correspondence:
Irena Andonova, BAS -- IEPP, Acad. G. Bonchev Str., bl. 25, Bg -- 1111 Sofia, tel. +359 2 979 2360; +359 886 391 855, e-mail: irena.and@gmail.com

 

Antiviral effects of interferon: 2. Interferon induced antiviral proteins - 46, 2010, No 1, 14-21.
M. Vasilev and Zh. Vasileva

Internal Diseases Clinic, University Hospital „Lozenets” -- Sofia
Summary: In the first part, we review briefly the history of IFN discovery, the mechanisms of IFN induction and secretion, the known IFN molecules and their receptors. In the second part, we review the molecular biology of the known ISGs with proven antiviral effects -- МхА protein, ISG 15, PKR and OAS-RNAase L.
Key words: interferon types, alpha, beta, gamma, omega, lambda, innate immu­nity, antiviral immunity, МхА protein, ISG 15, PKR, OAS-RNAase L
Address for correspondence:
Milen Vasilev, M. D., Internal Diseases Clinic, University Hospital „Lozenets”, 1, Koziak Str., Bg 1407 -- Sofia, e-mail: milen_vassilev@hotmail.com

 

Cysts of the jaws - 46, 2010, No 1,   22-29.
P. Pechalova(1), A. Bakardzhiev(2) and Z. Zapryanov(3)

(1)Maxillofacial Surgery Department, Faculty of Dental Medicine, (2)Oral Surgery Department, Faculty of Dental Medicine, (3)General and Clinical Pathology Department, Medical University -- Plovdiv
Summary: The authors follow up in chronological order the processes of accumulation of knowledge about cysts of the jaws, submit an actual classification, discuss a pathogenesis and some clinical and X-ray jaw cysts features.
Key words: cyst, mandible, maxilla
Address for correspondence: Petya Pechalova, M. D., Maxillofacial Surgery Clinic, UMHAT „Sv. Georgi”, Medical University, 66, Peshtersko shose Str., Bg -- 4000 Plovdiv, GSM +359 898 468 498, e-mail: pechalova@abv.bg

 

Adverse drug reactions - 46, 2010, No 1, 30-39.
R. P. Nikolov
Department of Pharmacology and Toxicology, Faculty of Medicine, Medical University -- Sofia
Summary: Adverse reactions to drugs are common problem of the daily medical practice. An adverse drug reaction is defined as any noxious and unintended response to the drug, occurring at doses normally used for therapy, prophylaxis or diagnosis of disease. Age, female gender and the number of drugs taken concomitantly are the most important risk factors for adverse drug reactions. Adverse drug reactions are classified into two main groups: type A (augmented reactions), and type B (bizarre reactions). Adverse reactions of type A may affect anyone and are related to the pharmacological action of the drug. Adverse reactions of type B occur only in susceptible patients and are unrelated to the pharmacological action of the drug.
Key words: adverse drug reactions, type A adverse reactions, type B adverse reactions, risk factors, side effects, toxic effects, allergic reactions
Address for correspondence:
Rumen Nikolov, M.D., Ph.D., Department of Pharmacology, Faculty of Medicine, Medical University, 2, Zdrave Str., Bg -- 1431 Sofia, tel. + 359 2 91 72 621, e-mail: ru_nikolov@abv.bg

 

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