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CURRENT ISSUE /2-2010

ASSOCIATION BETWEEN BIOCHEMICAL MARKERS
OF BONE TURNOVER AND MARKERS IN THE ESTROGEN RECEPTOR (ER) GENE

Zh. Ivanova(1), А. Toshev(1) and К. Tsachev(2)
(1)Department of Biology, Medical University – Sofia, Bulgaria
(2)Department of Clinical Laboratory and Clinical Immunology, “Alexandrovska”
Hospital, Medical University – Sofia, Bulgaria

Summary. Bone metabolism is characterized by two opposite activities: the formation of new bone by osteoblasts and the degradation of old bone by the osteoclasts. Osteoporosis is a disease in which subtle modifications of bone remodeling can result in a substantial loss of bone over a prolonged period of time. The needs for non-invasive techniques that can be applied more widely and repeated several times in a single patient explain the development of markers of bone turnover that are measured in blood and urine. The prognostic value of parameters as risk indexes for osteoporosis is not enough. This makes it possible to use genetic markers, which together with already existing risk indexes will improve the identification of individuals with higher osteoporosis risk. The future development of genetic studies in osteoporosis will proceed in two major directions: identification of further candidate genes, their interaction with each other and their application to defined diseases of bone metabolism.
Key words: osteocalcin, deoxypyridinoline, estrogen receptor (ER), bone mineral density (BMD)

 

COST MINIMIZATION ANALYSIS OF INHALLED
CORTICOSTEROIDS CONTAINING BECLOMETHASONE DIPROPIONATE FOR ASTHMA THERAPY

A. Stoimenova(1), V. Tzankova(2), M. Manova(1) and G. Petrova(1)
(1)Department of Social Pharmacy and Pharmacoeconomics
(2)Department of Pharmacology, Pharmacotherapy and Toxicology
Faculty of Pharmacy, Medical University, Sofia

Summary. Inhaled corticosteroids are recognized as the cornerstone of asthma therapy. They are considered the most effective anti-inflammatory medication currently available for the treatment of persistent asthma, regardless of its severity. The aim of our study was to assess the costs of beclomethasone dipropionate containing products for patients with asthma therapy in Bulgaria. Cost-minimization study was performed and the review of effectiveness was based on 5 randomized clinical trials found in search of PudMed, NICE, Cochrain library, and HTA databases. The pharmaceutical product prices were taken from the official register of the Ministry of Health. Amongst the pharmaceutical equivalent products, the prices per dose vary among 0,10 to 0,20 BGN that is a relative lower cost and it is also lower for generic products.
Key words: asthma, cost-effectiveness

 

PREGNANCY OUTCOMES IN WOMEN WITH TYPE 1 DIABETES TREATED
WITH LONG ACTING INSULIN ANALOGS. A CASE CONTROL STUDY

K. Todorova – Ananieva(1), E. Konova(2) and M. Guenova(3)
(1)High Risk Pregnancy Department, University Hospital of Obstetrics and Gynecology, Sofia, Bulgaria,
(2)Clinical Institute for Reproductive Medicine, Pleven, Bulgaria
(3)Department of Clinical Laboratory and Immunology, Medical University, Sofia, Bulgaria

Summary. The aim was to evaluate and compare the pregnancy outcome in women with type1 diabetes (T1D) intensively treated with long acting insulin or insulin analogs. A prospective two-year case control study in ninety pregnant women with T1D was performed. The intensified treatment consisted of insulin aspart as bolus insulin and long acting insulin as basal. Women were divided into three groups according to the basal insulin: n1=30 treated with NPH insulin, n2=30 treated with insulin detemir and n3=30 treated with insulin glargine. Participants were matched for age, duration of diabetes, BMI, HbA1c before pregnancy parity, number of previous pregnancies and abortions. Metabolic control, diabetic complications, severe hypoglycemic episodes and pregnancy induced hypertension and preeclampsia were registered. Perinatal mortality, stillbirth, macrosomia, weeks and route of delivery and neonatal complications were also recorded. Statistical methods: ANOVA – with multiple comparison and chi square test have been used. No statistically significant difference in mean values for age, diabetes duration, BMI, parity, and number of previous pregnancies. No differences were observed in pre-prandial, postprandial glucose and HbA1c levels in early pregnancy (HbA1c n1 = 7.3 ± 0.8%, n2 = 6.9 ± 0.9%, n3 = 7.1 ± 0.8%, P = 0.7). No differences were observed in postprandial glucose and Hba1c in late pregnancy (HbA1c n1 = 7.8 ± 0.3%, n2 = 7.3 ± 0.6%, n3 = 7.7 ± 0.7%, P = 0.06) as well. The level of preprandial glucose in late pregnancy was lowest in first group (n1 = 4.5 ± 1.4 mmol/l, n2 = 6.6 ± 1.1 mmol/l, n3 = 6.9 ± 0.8 mmol/l, P = 0.0001). The doses of short acting insulin were significantly higher in the first group in early (n1 = 25.9 ± 34.5 U/kg, n2 = 17.0 ± 25.3 U/kg, n3 = 19.6 ± 26.7%, P = 0.004) and in late pregnancy (n1 = 41.1 ± 20.0 U/kg n2 = 26.1 ± 12.9 U/kg, n3 = 21.9 ± 10.1 U/kg, P = 0.0001). There were no differences in the dose of long acting insulin in early pregnancy between the groups, but in late pregnancy the dose in n1 group was statistically lower in comparison to the other two groups (n1 = 16.0 ± 6.8 U/kg n2 = 21.4 ± 8.2 U/kg, n3 = 29.7 ± 6.6 U/kg, P = 0.001). Severe hypoglycemic episodes in the first group were observed at rate 16% (P = 0.03). There were no differences in frequency of hypoglycemic episodes between groups n2 and n3. Caesarean section was the main choice in all groups. There was statistically significant difference in the time of delivery in the third group compared to the other groups (n1 = 36.7±1.1 week n2 = 36.2 ± 1.2 week, n3 = 37.5 ± 0.7 week, P = 0.001). The newborn’s body weight in third group was statistically higher than in the other two groups (n3 =3623.9 ± 527.8 g, n1 = 3364.3 ± 662.4 g, n2 = 3076.7 ± 798.7 g, P = 0.02). The incidence of Respiratory Distress Syndrome was higher in the first group (P = 0.04). The frequency of neonatal hypoglycemia was higher in the third group (P = 0.003). The frequency of spontaneous abortion and stillbirths was higher in the third group, but without statistical significance. The evaluations of risk factors could not establish relationship between the observed fetal complications and the insulin treatment. It is concluded that the treatment with long acting insulin analogs during pregnancy shows similar maternal efficacy and safety. In terms of fetal complications and safety, the conduct of longer treatment trials in larger groups is needed.
Key words: low-impact insulin analogues, diabetes mellitus type 1, pregnancy

 

EFFECT OF ADMINISTRATION OF SURFACTANT THERAPY IN NEWBORNS
WITH NEONATAL RESPIRATORY DISTRESS SYNDROME

A. Jordanova(1), A. Tsanova(2), Y. Dumanov(3), D. Chakarov(4), G. Georgiev(3), E. Christova(5), C. Vassilieff(6) and Z. Lalchev(3)
(1)Institute of Biophysics, Bulgarian Academy of Sciences, (2)Faculty of Medicine, Sofia University “Sv. Kl. Ohridski”,
(3)Faculty of Biology, Sofia University “Sv. Kl. Ohridski”, (4)”Sheynovo” Hospital,
(5)Faculty of Public Health, Medical University – Sofia, (6)Faculty of Chemistry, Sofia University “Sv. Kl. Ohridski”

Summary. The aim of the present study was to compare the physiological condition and the maturity of tracheal aspirates from children with untreated neonatal respiratory distress syndrome (NRDS), and NRDS infants after therapy with the exogenous surfactant Curosurf. Pure Curosurf dispersion was tested for control. For this purpose biochemical and biophysical analyses of the clinical samples (before and after administration of Curosurf) were made. The lipids and the proteins concentrations of the samples were measured. In addition, the surface characteristics: equilibrium, and maximal and minimal surface tension values during 10 cycles of compression-decompression, as well as the shape of the hysteresis loop in the dynamic conditions were determined by using the pending drop method. Our results showed that the children with untreated NRDS had low phospholipid content, high equilibrium, maximal and minimal γ values. In contrast, the clinical samples from children, treated with Curosurf, showed high phospholipid concentration, and low surface characteristics, suggesting that the application of the exogenous surfactant improved the composition and the properties of the pulmonary surfactant in the infants. The results from our work could be useful for the clinical practice in the RDS therapy of children and adults.
Key words: respiratory distress syndrome, surfactant preparations, curosurf, method of pending drop, surface tension


WEB APPLICATION OF HEALTH DATABASE OF VITAMINS – ANTIOXIDANTS
Zh. Vinarova(1), P. Mihova(2) and I. Penjurov(3)
(1, 2, 3)Department Biomedical Sciences
New Bulgarian University

Summary. This article is dedicated to an authors’ realized product - a specialized online database, which is a separate operating unit of Telemedical System “TELE – “AntiOxi DB”. It is a new version of our previous development “AntiOxi DB” for vitamins with proven antioxidant activity. The updated version performs an online access. To offer such specialized information, an operational medical (or hospital) information system is needed that can be enriched by telemedical service for vitamins - antioxidants. Such specialization is very prospective, in combination with the increased health culture and modes of network communication. The benefits for users - experts and patients or health insurance specialists, do not require any comment. Periodic, preliminary announced and followed update information on vitamins with antioxidant focus becomes a representative and impressive part of the unit, where Telemedical Information System and a modern version of “good practice”operates.
Key words: database, vitamins, antioxidants


NUTRITIONAL ASPECTS OF SELENIUM (SE)
B. Ruseva(1) and F. Ribarova(2)
(1)Medical University – Pleven,
(2)Medical University – Sofia

Summary. The aim of this study is to present the current scientific achievements in the knowledge on selenium in order to enable the focusing on the specific aspects of the issue to the nutrition dimension. The cumulation of more specific data is important for reaching greater effectiveness of food and nutrition implementation in prevention of selenium deficiencies. Information is presented on the biological role of selenium, effects of selenium deficiency, selenium nutritional forms, Se content in various foods, recommendations for daily Se intake, Se intake of the population from some European countries and on selenium safety. The analysis of available current scientific evidence reveals numerous disputable issues and provides sufficient data for implementation of an adequate preventive policy complying with the specifics of the population groups and their geographic origin.
Key words: nutrition, selenium


EDUCATIONAL PROJECT ON FOOD SUPPLEMENTS FOR COMMUNITY PHARMACISTS
A. Stoimenova(1), M. Manova(1), A. Savova(1), T. Kundurzhiev(2), M. Stoycheva(2), S. Georgieva,
M. Dimitrova(1) and G. Petrova(1)
(1)Department of Social Pharmacy, Faculty of Pharmacy, Medical University – Sofia,
(2)Department of Social Medicine and Health Management, Medical Faculty,
Medical University – Sofia

Summary. Objective was to present and analyze the results of an educational program for community pharmacists on food supplements and to estimate the pharmacists’ needs of specific knowledge with regard to consumers’ counseling on food supplements. Anonymous questionnaire was distributed amongst the participants in order to complete the program gathering information on use of food supplements by pharmacists, their educational needs and frequently used sources of information. The pharmacists evaluated program as well. In total, 176 pharmacists completed the program. Out of 176 participants, 163 questionnaires were received, each providing answer to more than 90% of the questions. 138 responders stated they use dietary food supplements. 141 of the respondents use package leaflets as main source of information, trade representatives are used by 98, marketing materials and other types of advertizing by 80 respondents. 63 pharmacists specified the following areas they needed specific information: product quality information (n = 31), interactions (n = 24), adverse reactions (n = 14) etc. Conclusion: The study confirms that the pharmacists need additional knowledge about the content, manufacturing conditions and safety of food supplements in order to counsel consumers on food supplements. The adequate training of pharmacists shall be an integral part of every state policy on ensuring safety use of food supplements.
Key words: continuing education, pharmacy practice, food supplements, alternative medicine, pharmacy education, Bulgaria

 

MECHANISM OF TRANSACTIVATION BY EAD BASED ON PROTEIN-PROTEIN INTERACTION STUDIES
R. Todorova
Institute of Biophysics, Bulgarian Academy of Sciences

Summary. The Ewing’s Sarcoma Oncogene (EWS) on chromosome 22q12 is encoding a ubiquitously expressed RNA binding protein with unknown function that is target of tumor-specific chromosomal translocations in Ewing sarcoma tumor, clear cell sarcoma, myxoid liposarcoma, malignant melanoma of soft parts and desmoplastic small round cell tumor. A mechanism of trans-activation by EAD was proposed, based on protein-protein interaction studies. The complex Rpb4/7 binds to the N-terminus of EAD via Rpb7, thus connecting it to the Core RNA Pol II. The DNA-binding domain, provided by the ATF1, is bound to the promoter. The trans-activation by EAD can help to understand the mechanism of carcinogenesis that is related to the treatment of cancer.
Key words: Ewing’s sarcoma, RNA Pol II, transactivation by EAD

 

ACQUIRED GRANULOMATOUS HAEMORRHAGIC DERMATOPHYTOSIS OF THE BEARD DUE TO TRICHOPHYTON RUBRUM –
UNUSUAL CLINICAL AND HISTOPATHOLOGICAL PRESENTATION IN A GERMAN MAN

J. Patterson(1), G. Tchernev(2), J. C. Cardoso(3) and M. M. Ali(4)
(1)Division of Surgical Pathology & Cytopathology, University of Virginia, University of Virginia
Hospital Health System, Charlottesville, VA, USA
(2)Department of Dermatology, Venereology and Dermatosurgery, MVZ Kirchheim, Germany
(3)Dermatology and Venerelogy Department, University Hospital of Coimbra Praceta, Portugal
(4)Department of Dermatology and Venereology, Cardiff University, Cardiff, United Kingdom

Summary. Tinea barbae is an acquired dermatophytosis of the beard. It occurs worldwide with a higher incidence in agricultural areas, particularly in patients who have close contact with farm animals. Tinea barbae affects the hair and hair follicles of the beard and mustache. Dermatophytic fungi cause human infections worldwide. The fungal agents such as Trichophyton rubrum are contracted through occupational exposure to various animals that have been infected with zoophilic dermatophytes. Definitive diagnosis requires a combination of clinical experience, direct microscopic examination, culture confirmation and histological analysis. We report a patient who developed painful indurated plaques on the neck and the left cheek, with a tendency towards confluence. Based on the histopathologic and mycologic findings, the diagnosis of an uncommon granulomatous haemorrhagic form of tinea barbae due to Trichophyton rubrum was made. Treatment with 4 cycles of Itraconazol led to a durable remission of the disease.
Key words: Tinea, folliculitis, dermatophytes, onychomycosis, Itraconazole

 

ANAPLASTIC LARGE CD30-POSITIVE ALK-NEGATIVE Т-CELL LYMPHOMA OF THE SKIN-TREATMENT
OPTIONS: CURRENT STATE AND FUTURE DIRECTIONS

H. Okamoto(1), L. Arseniev(2), J. C. Cardoso(3) and G. Tchernev(4)
(1)Department of Dermatology Kansai Medical University 10-15 Fumizono, Moriguchi Osaka 570-8507, Japan
(2)Qualified Person & Transfusion Medicine Cytonet Hannover GmbH Feodor-Lynen-Str. 21, 30625 Hannover, Germany
(3)Dermatology Department University Hospital of Coimbra Praceta Mota Pinto 3000 075 Coimbra, Portugal
(4)Department of Dermatology, Venereology and Dermatologic Surgery, MVZ Kirchheim,
Steingaustraße 13, 73230 Kirchheim unter Teck, Germany

Summary. CD30+ lymphoproliferative disorders are the most common group of cutaneous T-cell lymphomas after mycosis fungoides and its subtypes. This group includes lymphomatoid papulosis and CD30+ anaplastic large-cell lymphoma. The molecular pathogenesis of these cutaneous T-cell lymphoma types has not yet been studied in detail. ALCL of T-cell type are a spectrum of disease ranging from primary cutaneous to systemic nodal ALCL. The systemic nodal ALCL is further subdivided into anaplastic lymphoma kinase-1 (ALK-1) positive or negative. ALK-1 protein is a gene fusion product of translocation (2; 5) and carries important prognostic implications. We present an unusual manifestation of cutaneous ALK-1-negative CD30-positive ALCL and discuss the current and future therapeutic options. When primary cutaneous CD30+ L (large) – CL is suspected, it is important to conduct a thorough systemic evaluation for systemic CD 30-positive and immunohistological studies for CD30-types. Ruling these conditions out will prevent unnecessarily aggressive treatment for primary cutaneous anaplastic large CD30+ lymphoma, an indolent disease with a favorable prognosis.
Key words: anaplastic, denileukin, MTX, c-Flip, trail, CTCL

 

A CLINICAL CASE WITH PMM2-CDG AND DANDY-WALKER MALFORMATION
M. Stancheva(1), I. Kremenski(2), M. Apostolova(3) , J. Jaeken(4), E. van Schaftingen(5), G. Matthijs(6),
N. Ivanova(3), V. Bojinova(7), B. Radeva(8), P. Perenovska(1), K. Vladimirova(2), R. Vajarova(2) and D. Todorova(7)
(1)Department of Pediatrics, University Children`s Hospital “ Alexandrovska”, Sofia, Bulgaria
(2)National Genetic Laboratory, Sofia, Bulgaria
(3)Bulgarian Academy of Science, Laboratory for Medico-biological Research
(4)Center for Metabolic Disease, Katholieke Universiteit, BE-3000 Leuven, Belgium
(5)Laboratory of physiological Chemistry, Institute of Cellular Pathology and University of Louvain, Brussels, Belgium
(6)Center for Human Genetics, Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium
(7)Department of Neurology, University Hospital of Neurology and Psychiatry, “Sv. Naum”, Sofia, Bulgaria
(8)Department of Pediatrics, University Children`s Hospital “Sv. Evdokia”, Sofia, Bulgaria

Summary. The authors report a 6-year-old boy with PMM2-CDG who presented with mild mental retardation, microcephaly, facial dysmorphysm, concomitant convergent strabismus, pseudobulbar, cerebellar and epileptic syndrome, inverted nipples, inguinal hernia, cryptorchidism, pectus carinatum. The MRI in the early childhood period showed Dandy-Walker malformation. The diagnosis was revealed with IEF of serum transferrin and confirmed with capillary zone electrophoresis. In cultured skin fibroblasts, the patient exhibited deficient phosphomannomutase (0.9 mU/mg protein). The sequence analysis showed compound heterozygosity for the common R141H/V231M mutations.
Key words: PMM2-CDG, Dandy-Walker malformation

 

PANAMERICAN CENTRE OF PATHOLOGY AS A BASIS OF PROGRESS
OF PANAMERICAN PATHOLOGY IN THE FUTURE

Al. N. Zubritsky
Department of Pathology, Municipal Institution “Taldom Central Regional Hospital”,
Taldom, Russian Federation

Summary. Nowadays in the American continent the necessary conditions seem ripe for the creation of a Panamerican Centre of Pathology which could function as a “brain” centre and at the same time be an office of the American continent’s pathologists. The process of organizing the Panamerican Centre of Pathology is proposed in the form of brief outlines and considerations for scrutiny and analysis to be followed by a thorough discussion. The creation of such a Panamerican Centre of Pathology which would have no counterpart in the world’s pathoanatomical practice will undoubtedly be a powerful breakthrough in Panamerican Pathology.
Key words: Panamerican Centre of Pathology, panamerican pathology, Panamerican Pathoanatomical Service

 

FREQUENCY OF ROOT CURVATURES IN MOLARS – AN IN VITRO STUDY
E. Boteva
Department of Conservative Dentistry, Faculty of Dental Medicine, Sofia

Summary. Root canal curvatures are often the main reason for a poor root canal treatment. The clinical x-ray images often do not give a precise view of the degree of the root curvature from the axial axis. The aim of the present study was to measure the severe curvatures > 25º separately for upper and lower jaw in representative number of extracted human molars. The length of each root was measured from the respective cusp for all 771 roots. All deviations were measured in the apical half of the roots, and registered when higher then 25-30º. The data shows that 47 of 461 upper teeth (10%) and 49 of 312 lower teeth (15.7%) were with severe curvatures. The highest numbers were found in lower third molars – 19.2%. In Bulgaria, root lengths are lower, than in the commonly used tables. This two findings are proving the higher risk of iatrogenic mistakes during root canal treatment. We found diagnostic x-rays and a working hypothesis for curvatures of each root after the first half essential.
Key words: root, curvatures, molars

 

SIGNIFICANCE OF THE SIZE OF CLINICAL CROWNS OF MOLARS IN CARIOLOGY AND ENDODONTICS
E. Boteva
Department of Conservative Dentistry, Faculty of Dental Medicine, Sofia

Summary. All academic tutors in the preclinical and clinical teaching are facing the problem with non accurate cavity preparations. The mistakes are related not only to dental amalgam restorations but to aesthetic restorations and endodontic cavities too. The aim of the present study was to measure the proper actual sizes of the clinical crown of molars and their variability in favour of more accurate cavity preparation in cariology and endodontics. 313 molar teeth are included in the study and following lengths were measured: mesiodistal, buccolingual, and buccal crown hight. The differences with commonly used in Bulgaria local literature sources are significant. It can be useful for the practice some of the regular terminology in lectures and operative dentistry manuals to be reconsidered. Cavities with buccolingual size up to 1/3, convergence of cavity walls in cariology, and even the possibility of convergence in endodontic cavities is essential to be carefully revisied. Respecting the decreasing of the sizes of the crowns of human molars during evolution, due to modern food industry, will lead to better clinical decisions in favour of the most important treatment task: rare restoration replacement, lower ware rates, and lower rates of secondary caries.
Key words: clinical, crowns, molars

 
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