Book of abstracts "International Symposium at Faculty of Medical Sciences"
"International Symposium at Faculty of Medical Sciences" Announcements Faculty of Medical Sciences at Goce Delcev University, Stip organize International Symposium Current achievements and future perspectives in medical and biomedical research The Symposium will be held on 24th of November 2015 at the Multimedia center of the Faculty of Economics in Stip. The Symposium will be accredited by the Pharmaceutical Chamber of Republic of Macedonia.
Use of disinfectants and antiseptics in selected health institutions in Republic of Macedonia
Introduction - Intra-hospital or hospital infections are caused by organisms acquired during hospitalization of the patient and clinically manifest from 48 to 72 hours after their administration. Disinfection procedures, type and quantity of used disinfectant is directly related to the effects of their use. Objective – The aim of this study was to review of the use of antiseptics and disinfectants in selected hospitals in Republic of Macedonia over five years period, to make analysis of the amount of antiseptics and disinfectants consumed annually on each department in hospitals, to analyze of the total amount of consumed antiseptics and disinfectants in selected hospitals for five years and to compare the results to the microbiological data conducted periodically in each department in hospitals in Strumica, Ohrid, Veles, Stip and Kavadarci for five years. Materials and Methods - Data from the annual reports collected from hospitals in Strumica, Ohrid, Veles, Stip and Kavadarci over five years were used. Data from annual reports for disinfectants and antiseptics (Bactosal, Ecosal, Dezintal, Betadine, Hydrogen peroxide, Formaldehyde, Ethanol) used on the selected departments for gynecology, surgery and transfusion were collected. Data from annual reports collected from public health centers in Strumica, Ohrid, Veles, Stip and Kavadarci over five years were used. Routine testing period for microbiological controls in hospitals was 15 days. Results - The results indicate a significant reduction of contamination with conditionally pathogenic bacteria when disinfection is conducted according to the standardized procedures controlled by the IHI times established in each hospital from 2012. The number of conditionally pathogenic bacteria detected is reduced starting from 2012. The reduction of the quantity of disinfectant used is also noted from 2012. Conclusions - In general disinfectants and antiseptics are used optimally and correctly according to the needs of the hospitals investigated. The amount of disinfectants and antiseptics consumed comparing with the microbiological data indicates their rational utilization starting from 2012. Use of disinfectants according to the standardized procedures established by the IHI times allows current daily care for patients and staff in the hospitals investigated. The processed data from public health centers in Strumica, Ohrid, Veles, Stip and Kavadarci confirm the above and point out the precautions to be taken when conditionally pathogenic bacteria have been detected. It is pointed out the role of IHI times in the hospitals, as well as the role of hospital pharmacists. We would like to suggest the implementation of disinfection process validation as standardization measure as well as more often routine microbiological controls in the hospitals. Keywords - disinfectants, antiseptics, disinfection
Ectodermal Dysplasia, a Case Report: a Challenge for Prosthodontic Solution
Introduction: Ectodermal dysplasia (ED) is a hereditary disorder characterized by developmental disturbances of two or more tissues and structures (skin, hair, nails, sweat glands, teeth structures, eye lenses, parts of the inner ear and nerves) of ectodermal embryonic origin. Hypodontia or anodontia of the primary and permanent dentition, poorly developed alveolar ridges and improper мaxillo - mandibular relations are the most common oral manifestations. Management of patients with ED requires a multidisciplinary team approach. Case report: A 6-year-old girl with ectodermal dysplasia having a normal intellectual development has typical features of ED: square and bossing forehead, prominent supraorbital ridges, slightly pigmented and wrinkled eyelids, prominent and pointed ears, wide nose with anteverted nostrils, thin lips, and pointed chin. Hypotrichosis is characterized by almost no eyebrows, eyelashes and skin hairs; the sculp is covered with a wig. The skin is dry (hypohidrosis), thin, rough and shiny. Finger and toe nails are short, thick, striated and slow-growing. Decreased lower facial height, together with deep mentolabial and nasolabial folds contributed to an old-looking facial expression. Complete bilateral cleft palate was partially solved on 1.5 year of age, with remained oro-nasal communication and a presence of soft palate only. An alveolar ridge in the mandible is atrophic with deciduous canines destroyed by caries and carious deciduous and permanent molar teeth in the upper jaw (severe hypodontia). The gingiva is rather swollen, with dark red color especially around the teeth. Several functions of the oro-facial system such as mastication, swallowing and phonetics are disrupted. Treatment procedure: According to the patient’s age and clinical findings, removable complete over-denture prosthesis was the treatment of choice. Preliminary impressions were taken with appropriate stock trays and irreversible hydrocolloid material. Border molding was done with a thermoplastic material while the functional impressions were made with light body polyvinyl siloxane impression material using the custom trays. Maxillo-mandibular relations were recorded using temporary bases with wax rims. Artificial teeth, reshaped considering the child’s age, were arranged according to a balanced occlusion. Final trial was taken to verify vertical and centric relations, occlusion, phonetics and aesthetics. The maxillar and mandibular prosthesis were produced in the heat cure acrylic resin. The facial frontal and profile expression improved significantly with complete dentures. Conclusion: Correct maxillo - mandibular relations and normal function of the dento-facial system in patients with ED, can be established by the acrylic dentures. Prosthodontic treatment has a major impact not only on the aesthetics and functions, but on the psychological development and emotional condition as well. Keywords Cleft palate, Ectodermal Dysplasia, Hypodontia, Removable dentures
Alveolar socket preservation and shaping using temporary prosthetic construction – case presentation
Abstract Introduction - Postextraction bone resorption usually results in reduced, deficient and sometime even defective alveolar ridge compromising the fabrication, hygiene and esthetic of the gingival part of pontic design. The deficiency of the partial ridge due to bone resoption is normal and expected, but it,s intensity and shape can be improved with proper planning and fabrication of immediate temporary construction prior the tooth extraction. Objective - The aim of the study is to present and investigate the effect of alveolar socket preservation and partially toothless residual ridge shape using immediate fixed or removable temporary prosthetic construction in cases with single tooth extraction indication. Material and method – Immediate temporary removable single tooth denture (4 cases) or temporary bridge (3 cases) were fabricated in 7 patients with indication of tooth extraction. The specific element in both prosthetic constructions is a small false root (4-5 mm) inserted in the postextraction alveolar socket. This pseudo-root was periodically corrected and decreased in height every 2 weeks. Results – The prosthetic construction applied immediately after extraction protects the alveolar socket allowing undisturbed healing and ossification. The short pseudo-root inserted in the cervical part of the alveolus gives support and prevents collapse of the soft tissue. Recommended period for using temporary construction is 8-12 weeks. Conclussion – The benefit of this simple procedure is to achieve faster healing of the postextraction socket and desirable shape of the toothless area. The disadvantages are necessity for proper planning prior the tooth extraction, relatively long period for shaping of the alveolar ridge and frequent adjustments of the immediate temporary construction. Keywords alveolar ridge, alveolar socket, prosthetic rehabilitation.
Case Report : Oligoasthenoteratozoospermia, treatment with acupuncture
Background -. Oligoasthenoteratozoospermia (OAT) is one of the most common causes of male infertility. Although the sexual function may be normal, there is a reduced count of mainly dysfunctional spermatozoa3. This condition includes oligozoospermia (lowe number of sperm), asthenozoospermia (poor sperm movement) and teratozoospermia (abnormal sperm shape). The term oligoasthenoteratozoospermia is used when all three factors are present1. The quality of semen is affected by smoking cigarettes or marijuana, alcohol, medications, hormone preparations, variococele, infections, genetics or it can be idiopatic when the cause for the condition is unclear. Acupuncture is very often used to enhance male fertility. With acupuncture the sperm quality and production can be increased, hormonal factor can be corrected by restoring balance to the entire body and mechanical blockages can be dissolved or reduced.2 Purpose - The main purpose of this work is to show a case of oligoasthenoteratozoospermia, the results before and after the treatment with acupuncture and that acupuncture is totally safe and effective treatment in the cases of man’s infertility. Methods – The acupuncture treatment has been done in ‘Tong da Tang’ clinic for Traditional Chinese Medicine and acupuncture in Skopje by Prof. Dr. Zhu Jihe. The patient is 35 year old male diagnozed with oligoasthenoteratozoospermia according to the criteria of WHO and KRUGGER. The patient has done 7 treatments in a period of two weeks. The treatments have been done in a closed room on temperature of 25 degrees with duration of 35-40 minutes. The needles were sterile with 0.25x25mm dimensions, made by Wuijuiang City Medical Health Material Co., LTD. The acupoints that have been used in the treatment are: DU20 (BaiHui), RN12 (ZhongWan), ST25 (TianShu), RN6 (QiHai), RN4 (GuanYuan), ST26 (WaiLing), RN1 (HuiYin), DU1 (CnagQiang), BL32 (CiLiao), BL28 (Bang GuangShu), LI4 (HeGu), PC6 (NeiGuan), ST36 (ZuSanLi), GB34 (YangLingQuan), SP9 (YinLingQuan), SP6 (SanYinJiao), LR3 (TaiChong), KI3 (TaiXi) and KI1 (YongQuan). Results - The patient has made two semen analysis tests before and after the acupuncture treatment. The patient done the first test after abstination of 5 days, by sperm giving method – masturbation and was diagnozed with oligoasthenoteratozoospermia according to the criteria of WHO and KRUGGER. After the acupuncture treatment, the patient has done another semen analysis, a standard test by the criteria of WHO (fifth edition 2010) and the results were totally satisfying. The interpretation is: Brought in material analysis - ejaculate with complete liquefaction, without presence of mucous fibers, not noticeable oligozoospermia or asthenospermia (with moderate degree of agglutination of sperm). Normal ejaculate volume and normal viscosity. Note - indicated an increased presence of leukocytes. Acupuncture is moving the whole body toward better health, so the sperm is in better health too. Healthier bodies make healthier sperm.2 Key words – acupoints, acupuncture, infertility, oligoasthenoteratozoospermia, treatment
Oxidative stress, аging and antioxidants
Abstract The term oxidative stress is defined as a direct consequence of the increased production of the so-called free radicals accompanied with the decreased activity of the antioxidant defense system against them. The “free radicals theory of aging” was firstly proposed by Denham Harman in 1950. According to this concept, free radicals attack the susceptible cell structures continuously over the life, thus impairing their physiological functions. Moreover, it was suggested that the increased oxidative stress plays a crucial role in the pathogenesis of various chronic diseases associated with aging, such as cancer, neurodegenerative diseases, atherosclerosis, etc. Later, in 1970, Harman expanded the previous concept introducing the role of the endogenously generated reactive species in mitochondria in the oxidative stress phenomena. The findings that the mitochondrial DNA damage in mammals increases with age further supported the mitochondrial theory of aging. Therefore, it was concluded that the intrinsic generation of free radicals is an inevitable consequence of the consumption of oxygen and ATP production by mitochondria. Later on, Halliwell and Gutteridge renamed this theory in “oxidative stress theory of aging”, suggesting that aging and age-related diseases are not only caused by free radicals, but also by other reactive oxygen species. According to their theory, organisms age because of an accumulation of oxidative damage to the critical cellular components. For example, the DNA is continuously exposed to the oxidative modification. Consequently, reactive species may form a variety of DNA adducts via direct attacks or indirectly by initiating autocatalytic lipid peroxidation. The situation is further complicated knowing that the moderate levels of radicals are not only beneficial, but also essential, for exerting their functions in signaling pathways, inflammation, or immune response to pathogens. There are various enzyme systems whose functions are to remove and/ or repair DNA modifications in order for cells to maintain the necessary level of oxidative stress. Moreover, the oxidative damage can be worsened by a decreased efficiency of antioxidant defense mechanisms. The first line of endogenous defenses against reactive oxygen species includes antioxidant enzymes. The most significant ones are glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD). Genetic factors may affect about 25% of the variation in human life span. Among the antioxidant enzymes, the biggest role in longevity can be attributed to SOD2 and GPX genes. Up todate, there are more than 80 publications supporting the role of genetic variations in the regulation of the response to the oxidative stress. Finnaly, nowadays, in addition to the natural defense systems, it is generally believed that dietary antioxidants are able to increase the antioxidant protection, thus improving health and increasing cellular resistance to stress. While, there is growing evidence that changes in lifestyle (such as, moderate exercise, increased intake of dietary antioxidants, and reduced calorie intake) could improve health and increase longevity, the role of the synthetic antioxidant supplements in controlling optimal levels of oxidative stress remains still controversial. Keywords Аging; Antioxidant enzymes; Free radicals; Oxidative stress
Contemporary Microbiological Diagnostic Tests for Rapid Identification and Detection of Resistance of Mycobacterium tuberculosis
Tuberculosis (TB) occurs in every part of the world as a top infectious disease killer. In 2014, 9.6 million cases and 1.5 million deaths (140 000 children) from TB were registered. Over 95% of TB deaths occur in developing countries. The Millennium Development Goal target of halting and reversing the TB epidemic by 2015 has been met globally. TB incidence has fallen since 2000 and is now 18% lower, by an average of 1.5% per year. An estimated 43 million lives were saved through TB diagnosis and treatment between 2000 and 2014. Another Goal target is ending the TB epidemic by 2030. According WHO Director General, „Everyone with TB should have access to the innovative tools and services they need for rapid diagnosis, treatment and care. This is a matter of social justice, fundamental to our goal of universal health coverage”. In cases of drug-susceptibility, TB is a treatable and curable disease with a standard 6 month protocol of 4 antimicrobial drugs. In some cases, extensively drug-resistant TB, XDR-TB, a form of multi-drug resistant TB with weak responds including the most effective second-line anti-TB drugs. About 480 000 people developed MDR-TB in the world in 2014. Establishing, equipping, financing, and ensuring sustainability of appropriate laboratory networks are challenging, complex and expensive, but necessary for an effective response to the challenges of TB-HIV and drug-resistant TB (DR-TB) control. Beside classical methods for isolation, identification and susceptibility testing, Reference laboratories introduce new, rapid methods. New systems for isolation use selective, liquid media (BACTEC, MGIT), which enable final diagnosis in about two weeks. In 2012, for the first time, rapid diagnostic test GeneExpert (based on molecular technics was established in Republic of Macedonia. GeneXpert MTB/RIF is an automated, cartridge-based nucleic amplification assay for the simultaneous detection of TB and rifampicin resistance directly from sputum in under two hours. As a result of use of contemporary standards for detection, treatment and prevention of TB included in National program for control of TB, in connection with realization of the Program for control of TB financially supported with grant of Global fund to fight against HIV/AIDS, TB and malaria, from 2002 to date number of new cases with TB in Rebublic of Macedonia significantly decreased.
Introduction Lymphoepithelioma is a type of poorly differentiated nasopharyngeal carcinoma characterized by prominent infiltration of lymphocytes in the area involved by the tumor .Malignant neoplasms of the nasopharynx are rare, amounting to 2% of the head and neck tumors and to 0.25% of all tumors.1,4 They are more prevalent among males, in a 3:1 ratio when compared to females, and presents two peaks of incidence: young people under 30 years of age.There is an intermediate incidence in population in the Mediterranean basin. It suggests an association with genetic susceptibility, environmental factors and infection by the Epstein Barr virus (EBV). Case Report A 8 year old boy had a symptoms of nasal congestion, nasal obstruction . pain and fullness localized in the right ear, sleeping with open mouth, no history of nasal bleeding of visual disturbance ,headache ,tinnitus and conductive hearing loss on the both ( in the period of 3 mounts) ears, timpanometry results during our examinations were :Type B on the right and type C on the left ear. He had complains for these symptoms about few mounts ( 6 ) . On the examination with rigid endoscope 30 through left nasal cavity there was enlargement such as adenoid hypertrophy in the epipharynx ,surface was smooth and not ulcerated macroscopically .but rigid endoscopy through right nasal cavity was impossible due to excessive amounts of seromucous mucus. Routine blood investigations were normal. According to the age and symptoms , the decision was adenoidectomy and application of the ventilation tube Grommet on the right ear. Under general anaesthesia operation was performed and the specimen was sent for histopathology. Post op period was uneventful. Histopathology result was Lymphoepithelial carcinoma. After that CT scan was performed (asimetry on the level of the nasopharynx ,because of the presence of the tu formation ,and the reduction and obstruction of the air space in the level of naso and oro-pharynx. In parapharyngeal space bilateral enlargement of the lymph nodes are detected. After confirmation the patient was referred for the radiotherapy and chemotherapy in university hospital in Turkey.After radiation treatment the patient is in good condition. Disussion Epithelial tumors account for 85% of malignant tumors of the nasopharynx, and are divided by the World Health Organization (WHO) according to their differentiation and production of keratin, as: Type I -Carcinoma, Squamous Cell, Type II – Carcinoma nonkeratinized and Type III - undifferentiated carcinomas. Type II and Type III have a positive serological profile for EBV, characterized by the detectionof viral DNA and viral antigens in tumor cells and high antibody titer in patients affected by the tumor 1. The lymphoepithelioma, classified as Type III.The histologic type should be classified according to World Health Organization classification. Kew words – Lymphoepithelioma,Epipharyngeal tumor ,boys, radiation therapy
Incidence of breast cancer in Macedonia Stojanova, Dijana; Markovski, Velo - Faculty of Medical Sciences, UGD - Stip Abstract Introduction Breast cancer is an abnormal growth and uncontrolled division of cells in the breast. Breast cancer is the most common cancer among women in the country and the most common cause of cancer death in women. According to the WHO, breast cancer is the most common cancer in women worldwide, claiming the lives of hundreds of thousands of women each year. Purpose The purpose of this work is to determine the incidence of breast cancer in the Republic of Macedonia and setting relation in terms of the prevalence of this disease in the world. Materials and Methods Within this analysis, data were taken from the hospital in the region of the capital Skopje, which marks the most populated. These data represent the men and women suffering from breast cancer who were hospitalized. The data used were obtained from the Centre for Public Health, National Institute of Statistics - MAKStat base, Institute of Public Health, data taken from the organization Borka and International Agency for research on cancer - EUCAN. Results In Macedonia, breast cancer is the first of malignant disease in women. According to the Institute of Public Health , the incidence of breast cancer is about 696 / 100,000 cases , while mortality is 240 / 100,000 that is represented by the absolute values ​​of 147 men and 1280 women such cases in 2014, 225 men and 839 such cases in 2013 and 139 men and 2629 women such cases in 2012 . Breast cancer in men is found in about 6 % of cases respectively in 2014 there were 147 infected men. Most patients are from 50-59 years of age. Conclusion In Macedonia, breast cancer is the first of malignant disease in women. The country is a country with an average incidence rate, but with higher mortality. The number of cases of breast cancer has increased in 2014. Most cases of this disease is 50-59 years. In a small percentage of breast cancer are diagnosed and men with 6%. Keywords: breast cancer, disease incidence, Macedonia
Achievements and perspectives in formulation of stable immunoconjugate of the HER2-targeting trastuzumab – potential for rapid labelling with Gallium-68
Abstract Objectives: To synthesize and evaluate the immunoconjugate of the HER2-targeting trastuzumab with Galium – 68 using already established method of freeze dried kit formulation. Introduction: Trastuzumab (Herceptin®) is a humanized IgG1 monoclonal antibody which is approved for therapy of HER2 positive breast cancer. Good clinical results and improvement of the patient’s general condition makes it interesting for further conjugation, in order to increase the therapeutic effect of trastuzumab. With the development of radiopharmacy many efforts are made for formulation of stable conjugates with various bifunctional chelators, further labelled with radioisotopes (α, β and γ emitters). According to the literature, successful conjugation of trastuzumab is achieved with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), DTPA (diethylenetriaminepentaacetic acid), TCMC (1,4,7,10-tetra-(2-carbamoyl methyl)-cyclododecane), HYNIC (succinimidyl-6-hydrazino-nicotinamide) and DTPA derivate 1B4M-DTPA (2-(4-isothiocyanatobenzyl)-6-methyl-diethylene-triaminepentaacetic acid). Significant radiopharmaceuticals based on peptide and antibody for diagnostic and therapeutical purpose used different radioisotopes (99mTc/188Re, 67Ga, 177Lu, 90Y, 131I). Several studies have shown that already existing radiolabeled formulations, using beta and alfa emitters (90Y-DTPA-trastuzumab, 86Y-DTPA-trastuzumab, 177Lu-DOTA-trastuzumab, 227Th-DOTA-p-benzil-trastuzumab, 225Ac-trastuzumab) are potent against HER2 positive breast cancer. Our already obtained and published results related tothe method for ready to use production of freeze dried kit formulation of Rituximab imunnoconjugates for labeling with Lu-177 and Y-90 including preclinical assessment of three imunnoconjugates (p-SCN-Bn-DOTA, p-SCN-Bn-DTPA and 1B4M-DTPA ) including chemical characterization, animal imaging, biodistribution and toxicological studies, were good reason to have an indication to introduce the same approach for labeling HER2-targeting trastuzumab using 68Ga3+ under mild conditions without subsequent purification for PET imaging. Work progress towards objectives and achievements Progress results and research outcomes critical to work progress and achievements are listed under our project milestones, and referenced to project aims. Milestone 1: Standardize previously established method used for freeze dried kit formulation of Rituximab imunnoconjugates for HER2-targeting trastuzumabimunnoconjugates. Milestone 2: Conjugation of bifunctional chelators to targeting for HER2-targeting trastuzumab, and radiolabeling with Ga-68 (define the most appropriate immunoconjugate). Milestone 3: In vitro characterization and in vivo biodistribution of 68Ga-labeled conjugates. Significance: Already established method for freeze dried kit formulation of conjugated Rituximab antibody ready for labeling with Lutetium-177, Yttrium-90 for therapeutical purpose that is under the final phase of the evaluation provide good information to introduce the same method for labeling of for HER2-targeting trastuzumab. The simplicity and efficiency of labelling and the possibility of kit-based 68Ga tracer production without complex automated synthesis typical of multistep PET radiochemistry will greatly increase 68Ga PET access to hospitals, expanding the use of the 68Ga generator. In the same time give opportunity to work on the same or similar kit formulation using with Lu-177 for therapy. Key words:bifunctional chelators, breast cancer, immunoconjugates, radioispotopes, trastuzumab.
Oral Hygiene Level Maintenance among Dental Medicine Students
Abstract Introduction: Oral hygiene is one of the most important measures for the preservation and promotion of oral health. Not proper maintenance of oral hygiene leads to create dental plaque. Dental plaque of the teeth and gums is the major cause of diseases of the tissues such as tooth decay, sensitivity of teeth and tooth necks, sore gums, gum recession, loosening of the teeth as a result of periodontitis. Aim: The aim of this study was to determine the level of maintenance of oral hygiene among students of Dental medicine. Material and method: For the realization of this survey was made a questionnaire with 5 questions. In the survey were included 40 students from third year. In the same students, checks were made, where it was determined the condition of the teeth and plaque index. Results: Forty-five percent of students had a plaque index less than 0.6 which means that they maintain proper oral hygiene. Fifty-two percent had plaque index of 0.6 to 1.9 which means that they maintain good oral hygiene, but they should take adequate measures to promote their oral hygiene. It was determined unsatisfied level of oral hygiene among 2.5% of the students. Conclusion: As a general conclusion, the study showed that students of Dental medicine maintained good oral hygiene. Individuals who maintain proper oral hygiene have a small percentage of dental plaque and have less probability to develop diseases of the teeth and parodontium. Key words: Oral hygiene, dental plaque, teeth, students, plaque index.
„Where Nanotechnology and Nanomedicine meet – Applications and Potential Risks“
Abstract Most definitions describing concept of nanotechnology includes control, understanding, design, imaging, measuring and manipulating matter at dimensions between 1 and 100 nanometers. Nano-structure poses unique physical, chemical and biological properties exclusively due to its nanoscale dimensions, significantly different from the properties of bulk materials and single atoms or molecules. Gravity loses impact and importance, surface tension and Van der Waals constants has more importance in system of nano particles. Extremely small size enables nano particles to enter the human body through usual or unusual routes, pass through cell membranes, cross the blood-brain barrier and access new sites, interact with DNA or small proteins at different levels, in blood or within organs, tissues or cells. Nowadays nanotechnology is being used in a range of applications, with potential to be applied at any stage in food industry: production, processing, packaging, labelling, transporting, tracing, keeping the quality of food product and extend the product shelf-life. The use of nanotechnologies to solve medical problems can dramaticaly improve the quality of life. Nanomedicine has the potential to enable early detection, prevention and significantly improve diagnosis, treatment and follow-up of many diseases. Based on nano (bio) senzors, rapid and sensitive detection of pathogenic bacteria and trace levels of viruses in small sample volumes and lower costs than current in-use technologies are developed. Early detection enables accurate and prompt treatment. Likewise, sensors to detect biofilm formation by bacteria on surfaces are developing Over 70 products are under clinical trials, covering important diseases including cardiovascular, neurodegenerative, musculoskeletal and inflammatory (such as cancer, atherosclerosis, diabetes, eye diseasses, antimicrobial resistance, tissue engineering, Alzheimer disease, arthritis). Nanomedicine delivered over 70 products, including nano-delivery, pharmaceuticals, imaging, diagnostics and biomaterials. Researchers have developed "nano-sponges" that absorb toxins and remove them from the bloodstream, absorb free radicals, monitor the level of nitric oxide (which indicate inflammation, important to monitor inflammatory diseases) in the bloodstream. Nanomedicine is understood to be a key enabling instrument for targeted and regenerative medicine by delivering of drugs (increases efficiency and minimizes side effects), treatments, implantable devices, early diagnosis of cancers, accurate cancer imaging, cancer therapy and drug delivery. Multy drug resistant microorganisms present one of the most serious and increasing global, public health threat. This problem causes approximately 25,000 deaths each year and over 1.5 billion expenses in healthcare and productivity losses in Europe. New strategies to combat MDR are urgently needed and nanomaterials are very promising approach. Metal nanomaterials (silver, gold, copper, titanium, zinc, magnesium, cadmium and alumina) possess unique antimicrobial activities. Silver ions showed strongest bactericidal effect. Regenerative medicine based on tissue engineering is currently a great exciting challenge for science and industry. Nanoparticles are also used to stimulate the body’s innate repair mechanisms, artificial activation and control of adult stem cells and to deliver vaccine, allowing a stronger immune response Nanomedicine provides important new tools to deal with the grand challenge of an ageing population. Future applications of nanomedicine will be based on the ability to build nanorobots. These nanorobots could be programmed to repair specific diseased cells („genetic surgery“), functioning in a similar way to antibodies in our natural healing processes and elimination of bacterial infection. Intense research is going on to make changes in the DNA structure of human beings as it can bring about a way to cure gene-related diseases. Risks of nanotechnology are still unknown and unpredictable. Potential problem with is the lack of knowledge and understanding the impact these products will have on the nanoscale. Initial scientific studies showed negative effects on living organisms and a potential for serious threat to human health in connection with disposal of nanowaste and environmental contamination. Scientists are primarily concerned with toxicity, characterization and exposure pathways. Number of ethical and societal concerns raised, ranging from possible health risks of using or consuming nanoenabled products, intellectual property rights governing them, and the new challenges they may raise. There are concerns that strong economic competition may be taking precedence over scientific prudence when it comes to public health and the potential dangers of nanotechnology. However, currently the benefits of nanomedicine definitely outweigh the risks. Key words: antimicrobial, ions, nanoparticles, nanomedicine, nanotechnology.
Analysis of clinical features and complications in patients with β-thalassemia in the region of Strumica
Thalassemias are hemoglobinopathies and are hereditary deseases which are characterized by disturbance in synthesis of one or more polypeptide chains of globin. Thalassemias are type of anemia of quantitative nature, where synthesized chain of hemoglobin are with normal structure, but not in adequate quantities. β-thalassemia is a desease characterized by production of large quantities of α-chains which exceedes the production of β-chains, whereas β-chains accumulate and precipitate into precursors of red blood cells and change their permeability, which leads to lysis of red blood cells. Within Research Center for Genetic Engineering and Biotechnology (RCGEB) is operating national reference laboratory for hemoglobinopathies, founded in 1970, where over the past 40 years examined more than 30,000 individuals from our country. The analysis revealed that the average frequency of beta-thalassemia in Macedonia is 2.6%, of alpha thalassemia is 1.5%, delta-beta-thalassemia is 0.2%, while the share of Swiss type of hereditary persistence of fetal hemoglobin (HPFH) is 0.3%. AIM OF THE STUDY The objective of this study was to show the prevalence, or the presence, of a certain type of thalassemia in the region of Strumica, R. of Macedonia, the complications that arise in specific cases, and the diagnosis and treatment of this inherited disease, not only for successfully identifying the extent of the presence of thalassemias in this region, but also to display the patient status in this region. MATERIAL AND METHODS The target group for this research were registered patients with thalassemia from the region of Strumica. For that purpose, we processed medical histories of 29 subjects suffering from some type of thalassemia. All subjects which entered in this study were respectively coded in order to avoid violation of their privacy and were randomly selected. As a material for the research we used data from medical histories of the subjects of interest, and subsequently analyzed those data. Of all data we selected those who are significant for our research like geographical location, sex, age, type of thalassemia, blood tests values, comorbidities and complications from the disease. RESULTS AND DISCUSSION Analysis of the available data shows that the most of the patients had or have β-thalassemia type minor, followed by patients with β-thalassemia type major, then α-thalassemia, and only 2 patients with β-thalassemia intermedia. As far as geographical location we can conclude that the most of the patient came from the city of Strumica, while other patients are from rural suburbs of Strumica. As suspected, all significant blood parameters which are characteristic for thalassemias, such as Hgb, Er, MCV, MCH, HbF, HbA2, AST, ALT, and others, shows deviation from normal ranges. Also we found a lot of comorbidities and complication associated with β-thalassemias. All patients were treated with standard therapeutically agents and procedures, such as iron chelating agents, iron supplements and therapy with washed and filtered red blood cells. CONCLUSIONThe data analysis indicates the presence of many characteristic sympthoms and clinical manifestation of many features of thalassemias, which confirms the theoretical framework for this hemoglobinopathy. In many patients it is observed decline in values of hemoglobin, reduces number of red blood cells, and disruption of liver function, followed by decreased function of liver enzymes. Therapy that is administered to the patients is of basic character, a continuous blood transfusion in patients with milder form of thalassemia, and excess iron chelators, whilst in the patients with severe forms of thalassemia spelenctomy was performed. The results shows that the experimental group of patients present many comorbidities and complications they complains with the medical theory about thalassemia. Keywords Thalassemia, blood transfusion, anemia.
Cognitive behavioral program in treating insomnia among elderly patients
Introduction: Insomnia is a most common in elderly patients. World wide experience showed that Cognitive behavioral program in treating insomnia is one of the best effective model. Objectives: The present study aim to present clinical experience from University Clinic Nuremberg, Centre for Sleeping Medicine with application of Cognitive behavioral program in treating insomnia among elderly. Material and Methods: The sample consists of 22 patients with chronic insomnia (10 primary insomnia, 12 secondary insomnia; 16 women, 6 men; mean age 64.6 years) treated in two consecutive group sessions. Participants compliance was 82%. Treatment program was consists of: 6 Group meetings, 1 Activation week, with total duration during 10 week. It include: Sleep hygiene and stimulus control; Sleep restriction; Progressive Muscle Relaxation; Mental Relaxation, Cognitive restructuring; Light Therapy; Sport; Excursions and cultural program. In order to assess the results of the Sleep diary and for the total and possibly sub-scores of the questionnaires pre-post comparison were made with the Wilcoxon signed-rank test, as a non-parametric statistical hypothesis test used for comparing two matched samples. Statistical analyzes depending on the machining rate on subgroups (15 to 17 people).In order to asses : sleep quality, daytime sleepiness, depressive symptoms, cognitive performance, before and after the training, the participants were examined with Pittsburgh Sleep Quality Index, (PSQI); Epworth Sleepiness Scale (ESS); Beck Depression Inventory (BDI);Syndrome Short Test (SKT). In addition, sleep diary were conducted and completed an evaluation questionnaire at the last meeting of the patient. Results: The high attendance compliance of 82% indicates a great motivation of the participating patients. The decisive factor here is probably a high psychological strain caused. The "poor" sleep quality of our sample showed both psycho-metric (PSQI) and in the sleep diary (sleep efficiency: 67.7%). Of the accompanying symptoms mentioned above in a means "light" depressive symptoms could be objectified, whereas daytime sleepiness and cognitive impairment were on the clinical border relevance. Conclusion: The results of the pre-post comparisons lead us to the conclusion that sleep quality, daytime sleepiness, sleep time, and mood positively changed during the day among older insomnia patients under the described cognitive-behavioral group program. Is draw special-lift that just often complained of the elderly long sleep onset and increased daytime sleep were reduced. However, important parameters such as sleep efficiency and total sleep time were unaffected, suggesting the need for a more intensive therapy settings. Key words: cognitive-behavioral, program, elderly, insomnia.
Control of the psychiatric disorders in the Republic of Macedonia
CONTROL OF THE PSYCHIATRIC DISORDERS IN THE REPUBLIC OF MACEDONIA Ramov Leonid; Markovski Velo ; Faculty of medical sciences UGD – Stip, Macedonia Introduction: The Psychiatric disorders are a large number of disorders which affect the mental and the behavioral function. Their etiology is rarely affiliated with some organic disorder, rather with a subjective perception or a disorder originating on a molecular level in some parts of the CNS. For their pathogenesis the key mechanisms are related with the environment and the psycho-physical development of the individual Aims: How much are these disorders present in the Republic of Macedonia? How is the healthcare system in Macedonia handling these disorders? Materials and Methods: In order to answer our aims we collected date from the institute of public health of the Republic of Macedonia, whose research from 2011 yielded some useful information about the incidence and hospitalization, which was put in a table. We confirmed the politics of the WHO on the healthcare ministry website www.moh.gov.mk. And in order to compare the results we used similar data from the Center of disease control from the USA Results and Discussion: With the acquired data we got the number of patients being treated in the Republic of Macedonia and also that they are being treated by the standards of the WHO. We also found lack of information and public awareness of the people about these kinds of issues and also information about cases of a particular disease of this type. Compared with the data from the USA Center of disease control it had both the percentage about adults which is 18.5 of the population being affected and the population of children which is 13%. They also separated the racial groups. In our institute they only had info about patients visiting a doctor related to a mental disorder, which is 5,9% (148120) of the population and from whom 2,8 %(7035) are being hospitalized. These results are showed in the following tables and graphics. Conclusions: These disorders are present in Macedonia with a percentage of 5,9 % of the population in general and 2,8 of them are being hospitalized. The Healthcare of RM is dealing with these disorders according to the WHO and has a lower incidence then the USA according these results. The institute of public health of the Republic of Macedonia does not have published info about the number of reported cases for particular mental disorders. Key Words: Healthcare; Psychiatric disorders; Psychiatry; Republic of Macedonia;
Assessment of orthodontic treatment need among school children by using iotn (index of orthodontic treatment need)
INTRODUCTION. Dental treatment is carried out in order to improve dentofacial аesthetic, function and health of patient. Aesthetic is the main reason for treatment, therefore we have to decide which aesthetic norms should we follow when we are planning orthodontic treatment. Although no consensus was reached for individual and occlusal features that need to be assessed in order to ascertain the orthodontic treatment need. In modern literature are using multiple indices to improve treatment planning. One of these indices is IOTN (Index of Orthodontic treatment need), described by Brook and Shaw (1989) and amended by Richmond (1990) as a method to objectively assess the orthodontic treatment need. AIM. This index is used to assess patient eligibility for orthodontic treatment. MATERIAL AND METHOD. Examinees aged 12-16 years of both sexes occurred in the orthodontic practice with a desire to be treated. Each of them were given a questionnaire filled out before completing the clinical examination. Normative orthodontic treatment need was assessed clinically using IOTN index. RESULTS. 70% of examinees thought it definitely need orthodontic treatment, and 30% of them think that probably yes. In 60% of them, the irregularities of the teeth noticed parents, 40% irregularities them into notes their dentist. 60% of respondents were previously orthodontic treatment, while 40% of them never previously had orthodontic treatment. CONCLUSION. A significant difference was found between our assessment and self-assessment of the examinees in the attractiveness of their occlusion. For effective orthodontic treatment, in addition to professional evaluate it, subjective perception must be taken into consideration when formulating a treatment plan in order to ensure a final product that will satisfy expectations of the patient. Keywords: IOTN, aesthetic, function
Сomparison of volatile aroma compounds between cultivated and spontaneous flowering stems of Sideritis scardica Griseb. from R. Macedonia
The specific and particular aroma of montain tea (Sideritis scardica Griseb.) is maybe the most important reason of its wide use by the Balkan peoples. The composition of the volatile aroma components was defined in the dried spontaneous (S-S) and cultivated (S-С) flowering stems (homogenized samples from flower, leaf and stem) of S. sсardiсa, collected from 4 different localities in R. Macedonia in 2013. The analyses were made by gas chromatography – mass spectrometry (GC/FID/MS) on HP5-ms column and equipped with automated headspace system with heated syringe (HS) sampler. Thirteen individual components (8 monoterpenes representing 71.91-90.21% and 5 sesquiterpenes representing 2.52-23.69% of the entire volatiles) were identified as aroma components in S-S samples. The major components in all S-S samples were β-pinene (31.85-45.35%), α–pinene (20.68-41.75%), trans-сaryophyllene (1.65-21.73%) and limonene (1.21-8.40%). In the S-С sample of S. sсardiсa, twelve individual components were identified, 7 monoterpenes (88.10%) and 5 sesquiterpenes (9.18%). Prevailing components in tested S-С sample were β-pinene (44.39%), α-pinene (32.21%), limonene (8.77%) and trans-сaryophyllene (7.39%). There was almost no difference in the chemical profiles of the volatile aroma compounds between S-S and S-С samples. Сultivated sample exhibit very similar aroma compounds profile with the spontaneous flowering stems of S. sсardiсa. Keywords Sideritis scardica, aroma compounds, headspace, GС/MS-FID
Comparison of the procedure for registration of medicines in the European Union and the Republic of Macedonia
Registration is a necessary step which follows every pharmaceutical preparation before being sent to the market and becoming available to patients. The approval follows two stages, the first clinical stage which provides security, safety and optimization of dosage integratively used in the four steps of clinical trials, and the second phase that provides marketing authorization. There are four agencies which operate with the procedure for approval and regulation of drugs: EU Legislation - Eudralex, European Directorate for the Quality of Medicines and Healthcare (EDQM), European Medicines Agency (EMA), Heads of Medicines Agencies (HMA) in the European Union. Objectives – Literature review of drugs registration procedure in our country and its connection to the form and content in the available literature documentation for the medicines registration in the European Union. Materials and methods - Comparative methods are used to compare the available literature data on the registration of medicines. Used data is from the guide on the form and content of the common technical document (Presentation and format of the dossier Common Technical Document (CTD) Volume 2B) and the Law on medicines and medical devices in the Republic of Macedonia. Results - The main difference between the European and Macedonian legislation for the registration of medicines is that the European legislation through extensive guides, closely defines every part of the documentation. The entire documentation should be submitted in the format designated as common technical document, whose form and content is on the EMA website with a guide of 303 pages. Here, we explain each module in a detailed manner, ranging from font, text size, the length of the text, to the content of each section. Thus, each application takes the form of a standardized and uniform document. On the other hand, in the Republic of Macedonia there are no such guides, so the applications can exhibit significant variations in form and content. Conclusion - Registered drugs in the country are registered under the national procedure for the registration of medicines in the country, according to the Law on medicines and medical devices. The national procedure is controlled by the Drug Bureau. The Republic of Macedonia needs to adopt guidelines as bylaws with exactly defined form and content of each part of the documentation. Keywords: Eudralex, EDQM, EMA, law, registration, drugs
Analysis of the Pap test results in the area of Kriva Palanka
Introduction: Pap test is a method of early detecting cancerous processes in the uterus.The first Pap test in Kriva Palanka was made in 1974, which was performed by doctors of General Medicine, till the opening of the Gynecological - Obstetric Department. Purposes: The purpose of the work was to make comparison of the positive results of the Pap test between different age groups. Materials and methods: For this purpose it is used an epidemiological method with a retrospectively study. Two age groups are being analyzed. In the first group there are women patients at the age of 49 to 60 years and the second group are the women patients at the age of 24 to 35 years. The screening of the first group is made in 2014 and of the second group in 2015. Because the year 2015 hasn’t finished yet, only the data of the first 9 months for both years are being analyzed. The data are from the Gynecological - Obstetric Department d-r Goran Mladenovski in Kriva Palanka. The results and discussion: From 1st January 2014 to 30th December 2014 there are totally 493 woman patients, from which 397 are in the first 9 months who came for screening of detecting cancer of the uterus. In the second age group, from 24 to 35 years, there are 418 women patients who came in the first 9 months. ASC-US is found at 15 women patients in the older group, and in the younger group it is found in 7 cases; ASC-H is found in 2 cases in the older group, and in the younger group it isn’t found such findings. Endo CIN 1 is also found in 1 case, but only in the older group. Endo CIN 2 is also found in 1 case in the older group. In the older group HPV is diagnosed in 23 cases, and in the younger group it is diagnosed in 11 cases. In the older group CIN 1 is diagnosed in 45 cases, and in the younger group it is diagnosed in 13 cases. In the older group CIN 2 is diagnosed in 4 cases, and in the younger group it is diagnosed in 1 case. CIN 3 is found in 1 case in each age group. In the older group AGC is found in 8 cases, and in the younger group it is found only in 1 case, and CIS is found only in the older age group in 2 cases. According to the results, the total number of the positive results in the older group is 102 from examined 397 women patients (25,7%), and in the younger group is 35 from examined 418 women patients (8,4%). In the Republic of Macedonia the screening programme is established on 1st April 2012. Conclusion: In accordance with the positive Pap tests, it is determined statistically significant difference between the first and the second age group of the patients. In the older group of women patients, there are increased numbers of diagnosed high-risk pre-malignant lesions, in contrast to the younger group of women patients where the highest percent of the positive results are with low-risk cell changes. The screening programmes at the younger population help a lot for detecting low-risk pre-malignant lesions on time, which can be treated and stop their malignity.
Oxidative stress, oxidative DNA damage and prostate cancer
Production of reactive oxygen species (ROS) is an element of normal cellular metabolism, which have their physiological functions. The problem occurs when the balance is disturbed and the body enters the zone of increased oxidative stress. The state of iincreased reactive oxygen species (ROS) is a result of either increased ROS generation or a loss of antioxidant defense mechanisms A growing body of evidence suggests that the increased production of ROS is linked to the aging process and the etiopathogenesis of age-related diseases, such as cancer, heart disease, atherosclerosis and other cardiovascular diseases, degenerative brain damage (e.g. Parkinson's and Alzheimer's disease). Excess ROS is harmful to normal cells. The purpose is to show the relationship between the oxidative stress, oxidative DNA damage and the development of prostate cancer. In prostate cancer (PC), oxidative stress, natural key event characterized by supraphysiological ROS concentrations, has been identified as one of the pillars/basis of the phenotype of aggressive disease. Specifically, oxidative stress is connected to PC development, progress and response to therapy. Prostate cancer is mainly a disease of aging, with in most cases, occurs in men over the age of 55. Therefore, progressive inherent or acquired changes in cellular metabolism occurring over the years may play a very important role in the development of this disease. Many factors like diet, environmental carcinogens, and other inflammatory diseases have been linked to an increased risk of prostate cancer. The main focus is on the free radicals, their endogenous and exogenous sources, DNA damage (both nuclear and mitochondrial), damage to lipids and proteins by free radicals, the oxidative stress phenomenon, cancer, and the mechanisms of carcinogenesis. The potential role of ROS in the regulation of cellular processes, controlling the malignant transformation suggests understanding of the etiology and progression of cancer in general and prostate cancer in particular. It can open the door for development of new treatments for prevention and cure of cancer. Because of the fact that the cells of prostate cancer are undergoing oxidative stress, strategies that can take advantage of this increased oxidative stress may also provide improvements in therapies. Measurements of oxidative stress stand a challenge, due to the instability of the compounds and the variability of the mechanisms involved. Thus, although there is a strong correlation between oxidative stress and PC, clinical data are lacking.
Effect of kinesitherapy on static and dynamic balance in patient after vertebro-basilar system stroke
AIM: To assess the effect of a kinesitherapeutic methodology in a patient who survived an ischemic stroke in the vertebro-basilar system (VBS) during the post-acute stage. MATERIAL AND METHODS: The case studied a 62 years old female patient, who survived an ischemic stroke and pulmonary thromboembolism and was administered to kinesitherapeutic regimen of individual sessions, 3 times weekly for a month. The kinesitherapeutic methodology included exercises for the general performance status, exercises for improving the lower limbs strength, exercises for improving the static and dynamic trunk control from different starting positions. The following methods of evaluation of changes have been used for the functional performance status in the patient at baseline and after the kinesitherapeutic sessions: "Berg Balance Scale", "Timed Up & Go", "Five Time Sit-To-Stand" and the test „Sit-to-Stand per 30 sec”. RESULTS: After applied kinesitherepy the static and dynamic balance and the strength of the lower extremities were improved. CONCLUSIONS: The Case study has shown that the targeted methods of kinesitherapy for influencing the static and dynamic trunk control resulted in improved postural stability, balance and performance status in a female patient with VBS stroke. KEY WORDS: postural stability, balance, VBS ischemic stroke
HER2 Transgenic Mouse Models: A Way To HER2+ Breast Cancer Targeted Therapy
Breast cancer remains the second leading cause of cancer mortality in women worldwide despite major advances made in the recent years. About 20-30% of breast cancers cases show HER2 over expression and amplification which predicts poor prognosis. Though HER2 has been successfully targeted with anti-HER2 therapies including mAbs such as trastuzumab and tyrosine kinase inhibitors, resistance to trastuzumab is a major setback. Resistance is proposed to occur by steric hindrance of antibody binding to HER2, expression of mutant HER2 as well as increased PI3K/Akt pathway activation. Since there is need to develop better therapies, HER2 transgenic mouse models will contribute greatly to the search for these therepies. The aim of this review is to analyse HER2 transgenic mouse models and demonstrate their potential towards development of new targeted therapy. The first model evaluated was generated in 2003 using wild-type HER2 and the whey acidic promoter (WAP) under the C57BL/6 background. The mouse was injected with ID8/E2, ovarian tumor cells and there was no tumor rejection in the transgenic mice which indicated tolerance to HER2. On vaccination with five cycles of a robust HER2 DNA based vaccine, there was induction of the immune system in the transgenic mice which was shown by anti-HER2 antibodies and 33% of the transgenic mice were protected from tumor growth. Consistent findings were obtained using the FVB-huHER2 mouse model which uses the MMTV promoter. In both models tolerance was broken by DNA vaccination hence offering protection. A newer HER2+/PIK3CA mutant transgenic mouse using a Tet-inducible system for gene expression was described in 2013. It was shown that HER2+/PI3KCA expressing mice developed tumors with shorter latency compared to mice expressing HER2 or PI3KCA mutant oncogene alone. Cells from HER2+/PI3KCA tumors showed more lung metastases in the nude mice and the tumors were resistant to trastuzumab alone or in combination with lapatinib. Resistance was reversed by a PI3K inhibitor. This shows that increased PI3K activation has a role in trastuzumab resistance. The transgenic mouse models expressing human wild-type HER2 oncogene only is suitable for testing of vaccines while the HER2+/PIK3CA mutant transgenic mouse model is suitable for studying trastuzumab resistance and testing of PI3K inhibitors. HER2 transgenic mouse models therefore have great potential towards development of better targeted therapy. If new drug targets are to be identified, new HER2 transgenic mouse models will need to be developed. Key words: HER2, HER2 transgenic mouse, PI3K, targeted therapy, trastuzumab.
Mouse Models For Human Prostate Cancer: Xenograft Vs Genetically Engineered Mouse Model
Prostate cancer is among the commonest cancers in men with high mortality. It is thought to arise from accumulated genetic mutations that may transform benign prostatic epithelium to prostatic intraepithelial neoplasia (PIN). With additional genetic alterations, PIN progresses to invasive cancer, and finally to metastatic disease. Metastatic prostate cancer is generally accompanied by emergence of androgen-independent cancer. About 70% of primary prostate cancers exhibit a loss of at least one PTEN allele and loss of both alleles is associated with advanced disease. PTEN is tumor suppressor gene that works by suppressing the activity of Akt /PKB pathway. Over expression of many oncogenes has also been observed in many human prostate cancers. Animal models are crucial to understand the underlying biology and to test novel prevention and treatment strategies for prostate cancer. Appropriate animal models should recapitulate genetic alterations and clinical courses of human prostate cancer. The following paper describes important characteristics of genetically modified mouse model and xenograft mouse model. We performed recent literature search for human prostate cancer mouse models. Numerous mouse models of human prostate cancer have been generated and exhibit common characteristics of human prostate cancer. Initially, the immunocompromised mouse was used as a xenograft model for in vivo analyses of human prostate cell lines. This approach does not however consider the heterogonous nature of prostate cancer as a disease with complex interactions between the transformed cells, the resident cells, the stromal cells, the endothelial cells and the immune cells all which participate in the disease pathogenesis. One of the genetically engineered mouse models is the prostate specific Cre-mediated conditional expression of Myc oncogene by removal of a conditional STOP sequence (PB-c-Myc,).This model progresses to invasive carcinoma without metastasis. The other is a conditional PTEN Knockout model using Cre recombinase targeted to the prostate specific probasin promoter. This model recapitulates the human prostate cancer to metastasis carcinoma. Genetically engineered mouse models are more able to recapitulate the human prostate cancer compare to the xenograft. The PTEN knock out mouse is suitable for understanding molecular basis of the disease. Xenograft will remain more useful testing of therapy. In the future more sophisticated prostate animal model should be available so as to recapitulate the heterogeneity of the disease Keywords: Knockout, Mouse model, Oncogene, prostate cancer, Xenograft
Giant rhinophyma treated by excision and full thickness skin grafting
Rhinophyma is a slowly progressive, disfiguring disorder of the nose seen almost exclusively in men over the age of forty. It consists of large nodular masses of hypertrophic and hyperemic connective tissue and sebaceous glands. The supposed association with increased alcohol abuse often leads to psychological problems for the person concerned. Rhinophyma is the final stage in poorly controlled acne rosacea. Its etiology remains uncertain. Surgery is the most common treatment of choice. Different surgical procedures have been described, such as excision with primary suture or extirpation with plastic covering of the defect by free transplants, subcutaneous rhinophyma resection, as well as decortication with peeling off the proliferations, dermal abrasion, or dermal shaving. We report on a 72-year-old man presented with an unusually severe case of rhinophyma. The patient presented with a seven-year history of a progressively growing mass on the nose with a history of nasal obstruction and history of alchocol abuse. On examination, there was a large pedunculated mass measuring 7,5x7x5,5cm arising from the tip to the dorsum of the nose.The pedunculated mass was widely excised and a skin graft from the medial upper leg was applied. A very satisfactory cosmetic result was obtained.
Significance of preparation of tissue samples for electron microscopy for observation and diagnosis
Electron microscopy (EM) is used to provide descriptive, morphological information and plays important role in cell biology for the visualization of intracellular organelles. Electron microscope uses a beam of electrons to provide an image of the specimen. Two types of electron microscope are available; Transmission Electron Microscope (TEM) where electron beam passes through the specimen and objects of 1nm in size can be observed, and second, the Scanning Electron Microscope (SEM) where topographical information of the surface can be provided. Significance of preparation of the samples for EM requires precise execution of each step in the entire procedure. This presentation gives an overview of the variety of techniques that have been developed to prepare TEM specimen ready for observation and diagnosis. Following steps are crucial in sample preparations: extraction of tissue, fixation, dehydration, resin infiltration, embedding, ultramicrotomy and staining. If the tissue block is too large or if the sample is kept for a short period in fixative and resin, they will not penetrate to the middle of the specimen, and the tissue in the middle will be soft. This sample is not suitable for section on ultramicrotome. Generally, formaldehyde better penetrates into the tissue and glutaraldehyde better preserves the structure. After initial fixation, for the second fixative osmium tetroxide is used to preserve lipids. During dehydration step, water from the samples is removed by solvents such as ethanol or acetone. This prevents creations of holes in the sections. Infiltration and embedding in resin provides stability of the tissue sample and formation of indestructible and insoluble block, suitable for ultramicrotomy. Inadequate fixation, dehydration or infiltration of specimen leads to further tissue destruction, making it inappropriate for diagnosis. The aim of this study was to compare alternative procedures, for preparation biological sample for TEM. We found that method based on paraffin embedding of the samples has several disadvantages including disruption of continuity of the tissue. However, this method still can be useful for diagnostic purposes. Keywords: Sample preparation, TEM, paraffin embedding
Bioactive compounds of cold-pressed oil from the seeds of Goji Berry (Lycium barbarum)
Oral surgery treatment in the patients with combination syndrome
Abstract INTRODUCTION Combination syndrome isassociated with anterior hyperfunction syndrome. This syndrome isseen in patients with a completely edentulous maxilla and partially edentulous mandible with preserved some of the anterior teeth. MATERIAL AND METHOD The investigationwas provided on five patients with removable dentures at the Department of prosthodontics in the period of last three years. Three of them have weared the dentures more then ten years, and came to the clinic for new one. Another two patients have weared removable dentures between two and four years, and came because the frontal part of the upper jaw appeared swollen. By clinical examination in all patients we noticed hyperplastic tissue in the pre-maxillary region andreduction of the residual ridge on the frontal part of the maxilla as a result of the increasing pressure from the anterior teeth of thelower jaw.This tissue was removed by oral surgery (laser removing of hyperplastic tissue). Also we noticed periodontal changes and extrusion of natural lowerfrontal teeth and increased reduction of mandibular residual ridge. Results AND CONCLUSION After healing period we made new dentures in the three patients which were covered by the HIFM andin another two patients we made indirect relining on the upper denture, re-occlusion and re-articulation achieving a weak contacts between the lower natural teeth and upper teeth of the complete denture. We recommended the patients not to bite food with anterior teeth and to avoid chewing very hard food which tends to imprint and displace dentures and of course to came to regular controls. Key words: removable dentures, combination sindrom, hyperplastic tissue, oral surgery treatment
Production of [11C] Choline in The University Institute for PET – new perspective in diagnostics of prostate malignancy in R. of Macedonia
[11C] Choline injection is radiopharmaceutical for oncological PET imaging of tumors which overexpress choline kinase. The most important clinical application of this PET radiopharmaceutical is in prostate cancer that can be visualized precisely, having differentiated localization located in comparison with benign tissue. The uptake of specific radiopharmaceutical remains constant thereafter, allowing better visualization of this kind of tumor. [11C] Choline PET/CT could represent an important imaging modality also in the detection of distant relapses in prostate cancer patients with biochemical recurrence. The reason to have [11C] Choline in a first line of production is the evidence-based indications including also in a clinical guides: - Evaluation of equivocal findings on conventional imaging such as possible nodal or metastatic disease in patients with prostate cancer where confirmation or exclusion of distant disease would directly influence patient management - Suspected recurrence in patients with a rapidly rising prostate-specific antigen (PSA) and inderteminate or equivocal conventional imaging where the results would directly influence patient management. According to the short half-life of 11C radionuclide (t1/2=20.4 min), the production of [11C] Choline must be performed in PET facilities with on-site cyclotrons and should be as fast as possible to reduce the loss of activity due to decay. The University Institute for Positron Emission Tomography in Skopje is equipped with a cyclotron GE PETtrace 800 for production of 18F, 11C, 13N and option for solid targets. 11C that we are planned to use for [11C] Choline is produced by cyclotron as [11C]CO2 or [11C]CH4. 11C radionuclide, produced as a gas in one of these chemical forms, is being transported through stainless steel tube to the GMP production laboratory, where a hot cell for synthesis of [11C] Choline and a hot cell for dispensing are installed. MIP is shielded cell where the methylator and the module for carbon labelling CarbonSynton are placed in. BBST-PC Laminar Flow Hot Cell is equipped with Clio-volumetric dispenser which is designed to dispense both vials and syringes. The automatic compact injector system allows automatic intravenous infusion of radiopharmaceuticals in a radiologically safe manner and with maximum control of all critical parametres such as the flow, the amount and the injection time. The UI PET Skopje is the first center with all these opportunity in the Balkan region which has full equipment for production of [11C] Choline radiopharmaceutical. In our country where improving the health care system is one of the national imperatives, introducing [11C] Choline PET/CT as diagnostic procedure, will contribute to the strategy for better management of patients with prostate malignancy. Keywords [11C] Choline, cyclotron produced radiopharmaceuticals, PET/CT, PET radiopharmaceuticals, prostate cancer
Calculation of effective dose to family members of patients with thyroid diseases
Radioactive iodine 131I has been used for many years to treat benign thyroid disease. Treatment of thyroid cancer with 131I NaI is the most common application of radionuclide therapy in nuclear medicine and has been in use for many decades. At the Institute of pathophysiology and nuclear medicine at Skopje this kind of radiotherapy is performed since 1956y. Approximately 50 thyroid cancer patients and the same number hyperthyroid patients have been treated with radioactive iodine 131I every year. The patients, treated with radioactive iodine 131I present a radiation hazard to other individuals such as hospital staff, the patient’s family and members of the public with whom a treated patient may come in close contact. This situation can be overcome by imposing restriction on the behavior of the patient, to minimize the dose to close relatives and other individuals. In 1991, the International Commission of Radiological Protection (ICRP) has recommended a radiation constraint of 1 mSv/year to the general population. According to Basic Safety Standards Directive, the dose limits to the general public are not valid for “exposure of individuals, who are knowingly and willingly helping, other than as a part of their occupation, in the support and comfort of in-patient or out-patients undergoing medical diagnosis or treatment”. Proposed dose constraint from the BSS is: 0.3 mSv per episode for the public, 1 mSv for children, for the adults up to sixty years the dose constraint is 3 mSv and for adults more than 60 years old it is 15 mSv. The implementation of this guideline differs among various countries. In the Republic of Macedonia about fifty thyroid cancer patients are treated on in-patient basis and approximately fifty hyperthyroid patients is treated ambulatory on out-patient basis. According to the local hospital rule and old guidelines the maximum given activity to hyperthyroid patients, treated on out-patient basis, is 1110 MBq. The new, not yet established guidelines, proposed to reduce the maximum given activity to hyperthyroid patients, treated on out-patient basis, from 1110 – 555 MBq. This group of patient’s present great radiation hazard to their family members. Upon discharge from hospital, the patients as well as their family members were given brief radiation instructions. The aim is to minimize the transfer of radioactive material to person coming in close contact with patient. There are several papers in the literature concerning the subject of doses received by family members of thyroid cancer and hyperthyroid patients. Most of the published studies agree that doses to the family members are bellow the proposed dose constraint of 1 mSv. There are also several papers that present cases where children or other persons have received higher radiation doses than proposed dose limit and usually it is case with hyperthyroid patients and their close relatives. This study was undertaken to measure the effective doses to family members of patients treated with radioactive iodine 131I for thyroid diseases at nuclear medicine department in Skopje. The main purpose of this study was to estimate the radiation exposure to family members of hyperthyroid and thyroid cancer patients treated with radioactive iodine 131I and to calculate the effective dose according given activity using Radiation Dose Assessment Resource (RADAR) software. Keywords Effective dose, iodine, thyroid.
Incidence of patients with chronic renal failure
Incidence of patients with chronic renal failure in Skopje Simona Kamcheva, Markovski Velo Faculty of Medical Sciences, UGD– Shtip Introduction:Chronic renal failure it contains a large number of pathological processes, all of which are characterized by a gradal loss of kidney function. HBI main dysfunctions associated with decreased glomerular filtration rate <60 ml/min and loss of tubular function. Purpose:The purpose of this paper is to ascertain the incidence of patients with chronic renal failure on hemodialysis for the City of Skopje (of the Republik of Macedonia), for the period from 2012 to 2014. Material and methods: Centre for Public Health of the City of Skopje Institute of Public Health of the Republic of Macedonia University Clinic of Nephrology, Faculty of Medicine Skopje Macedonian Academy of Sciences and Arts, Skopje Results:In 2012 in Skopje,registered 1318 cases of chronic renal failure treated with dialysis, and according to data processed 50.5% were male and 49.5% were female. While in 2013 the numer of cases increased by a total of 328 infected people, whereas this year the percentage dominance belongs to the female (50.1% of the total infected people in 1646).In terms of 2013 in 2014 in Macedonia incidence of cases in which declines were registered in 1586 patiens, of which 804 are males and 782 are females. Declining incidence is likely due to fewer new patient with HKD on the one hand, and dead or displaced from Skopje on the other hand. Conclusion: The analyzed period , the City of Skopje in 2013 has the most registered patients on dialysis (1646) compared to 2014 and 2012. Has the highest incidence in the age group of 55-64, more patients are female. Used literature: -US Renal Data System: Annual Data REport: Atlas of End Strage Renal Disease in the United States, Bethesda, National Institutesof Health;http://www.usrds.org/adr.htm. -Владимир Серафимоски . Интерна медицина. Скопје, Катедра по интерна медицина. Македонска ризница Куманово. -Чарлс Д. Форбс, Вилијам Ф.Џексон. Клиничка медицина: атлас во боја и текстови (3-то издание).Скопје:Магор. Key words:chronic renal failure , prevalence, infected people .
Iatrogenic mistakes, cause for a failure at surgical treatment of a chronic periapical processes
Introduction: The chronic periapical processes are common changes that can be located in the oral cavity. One of the main reasons for their occurrence are untreated infected teeth, usually infected by caries, but also bad, late or incomple treatment of the root canals. According to numerous researches over 60% of all the surgical interventions are the surgical treatments of a chronic periapical processes and their consequences. The failure at the surgical treatment of the chronic periapical processes can show up as a result of iatrogenic mistakes, and sometimes the causes are some general or local factors. Aim: The aim of this research was to present some of the iatrogenic mistakes as a rear reason for the failure of the surgical treatment of the chronic periapical processes. Material, methods and results: In a 12 months period from August 2014 to July 2015, the surgical treatment of a chronic periapical processes was applied to 20 patients in different dental offices. Results: After a period of three months in 10 % of the cases (two patients) a failure of the treatment was found which led to an extraction of the apicoectomied teeth. Conclusion: The cause of the failure in these cases is the iatrogenic mistake which can be seen on the RTG that was made after the intervention. Keywords: iatrogenic, periapical.