Proangiogenic signature in advanced laryngeal carcinoma after microRNA expression profiling.

The aim of this study is to evaluate which dysregulated angiomiRs compose the specific proangiogenic microRNA signature of advanced laryngeal cancer and review the literature. Thirty-six samples from twelve patients with advanced laryngeal carcinoma were collected. Total RNA was extracted and microRNA global profiling was performed using Agilent Technologies Microarray Kit. Fifty-nine microRNAs were found to have significantly different expression levels. Eleven microRNAs from the whole group were sorted as regulators of tumor angiogenesis (angiomiRs): seven were up-regulated-miR-1246, miR-181b 5p, miR-18a 5p, miR-21 3p, miR-210 3p, miR-503 5p, miR-93 5p and four were down-regulated-miR148a 5p, miR-145 5p, miR-204 5p, miR-125b 5p. For none of those microRNAs we found heterogeneity in tumor tissue. We are the first to report the specific proangiogenic microRNA signature in advanced laryngeal carcinoma and we confirm and amplify findings from previous studies that expand our perception of a specific "molecular state" of angiogenesis that is distinctive only for laryngeal cancer.

Establishment of the first stool bank in an Eastern European country and the first series of successful fecal microbiota transplantations in Bulgaria.

OBJECTIVE: For safe implementation and broader application of fecal microbiota transplantation (FMT), quality controlled stool banking is a must. Establishing a stool bank is a complex, time-consuming, and expensive process, making it a real challenge in an Eastern European country. We aimed to establish the first stool bank in Eastern Europe - in Bulgaria. SUBJECTS AND METHODS: A multidisciplinary team of gastroenterologists, microbiologists, infectionists, and geneticists was set up. We used a questionnaire based on the First European FMT Consensus in order to recruit possible stool donors. Laboratory blood and stool tests were performed on all potential donors. RESULTS: Between October 2018 and April 2019, 112 donor volunteers completed a questionnaire; 70 (62.5%) were excluded, mainly because of age above 50, an unhealthy BMI, and risk behavior. Fourty-two (37.5%) donor candidates were invited for laboratory testing of blood and feces, of which 12 (28.6%) passed this screening. Of 12 donors, 4 (33%) failed at the following screening test, which is performed every 3-6 months. Finally, 8 (7.14%) active donors were enrolled. Ten successful FMTs were performed on patients with recurrent Clostridium difficile infection. CONCLUSIONS: Even though we found many healthy volunteers, only a low percentage (7.14%) of them were suitable to become feces donors. Establishing a stool bank in an Eastern European country is essential for making FMT safe and more popular as a treatment method, finding further implementation and regulation of FMT and supporting physicians offering this treatment to their patients.

A pharmacoeconomical model for choice of a treatment for pregnant women with gestational diabetes.

This study discusses two main questions: the direct medical costs and the clinical effectiveness of the hospital treatment with insulin of pregnant women with gestational diabetes (GD). A prospective study that includes 50 women with GD is performed. The pregnant women are divided into 2 groups: Group I (n=30) - pregnant women treated only with a diet; and Group II (n=20) - pregnant women treated with diet and insulin. We found that the metabolite compensation degree is improved after the applied treatment with insulin. The coefficient cost/effectiveness is 6954 lv./100 women. The analysis decision tree confirms in a very convenient way the fact that insulin treatment is a clinically more effective and financially more profitable strategy.

Pilot project for education of patients with type 2 diabetes by pharmacists.

The objective was to adapt and test an educational programme for type 2 diabetes patients. The sample consisted of 24 individuals with type 2 diabetes between 31 and 75 years of age that did not require insulin, without severe complications of diabetes. A patient satisfaction questionnaire was applied in the beginning and at the end of the survey. A five-month education was conducted on: hypo- and hyperglycaemia, nourishing and physical activity, feet care, eye care and possible adverse drug reaction. The costs of the education and the pharmacological treatment were calculated. Improvement was observed in patients' diabetes knowledge and there was a decrease in the frequency of hypo- and hyperglycaemic incidents (about 60% less). At the end of the programme no incidents were matched, saving Euro 10/patient. The benefit to cost ratio is about 1:1 (Euro 140:Euro 142.80). The patients' quality of life improved by about 5% according to the Diabetes Questionnaire (IMG). The educational approach has the potential to decrease diabetes complications and therefore the economic cost of type 2 diabetes. Introduction of the programme will benefit diabetes patients, promote pharmacies as a source of independent drug information and recognise pharmacists as competent healthcare providers.

Analytical studies of the Alexandrovo Thracian tomb wall paintings.

A profound study of samples obtained from Thracian tomb wall paintings at Alexandrovo, Bulgaria (dating back to the fourth century BC) were carried out by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and Attenuated Total Reflectance Fourier transform infrared spectroscopy (ATR FTIR), high-resolution transmission electron microscopy (HRTEM) and energy dispersive X-ray spectroscopy (EDS). The current work provides a glimpse of the ingenious construction and painting techniques used in Thracian tomb at Alexandrovo. The results suggest that beeswax was used as a paint binder and also revealed presence of various nano-materials.

Occupational exposure to lead and induction of genetic damage.

To investigate whether occupational exposure to lead is genotoxic, we evaluated data from 103 lead-exposed workers and 78 matched controls. These data correspond to three different sampling periods, and we measured genetic damage as increases in the frequency of binucleated cells with micronuclei (BNMN) in peripheral blood lymphocytes. The levels of exposure were determined according to the lead levels in blood. Clearly significant increases in BNMN were observed in the exposed groups when compared to the control group. In addition, for the overall population (n = 181), we observed a clear relationship between lead levels in blood and BNMN (r = 0.497; p < 0.001). When we examined four exposure levels--very low exposure (< 1.20 microM/L), low exposure (1.20-1.91 microM/L), high exposure (1.92-2.88 microM/L), and very high exposure (> 2.88 microM/L)--we found significant differences in the genetic damage induction. We conclude that exposure to levels of lead higher than 1.20 microM/L may pose an increase in genetic risk. In addition, our data show that blood lead level is a good indicator of genetic damage induction.

Phospholipid black foam films: dynamic contact angles and gas permeability of DMPC bilayer films.

The behavior of bilayer Newton Black Films (NBF) from aqueous dispersions of dimyristoylphosphatidylcholine (DMPC) have been studied in dynamic conditions. The dynamic contact angles theta and the gas permeability coefficient K have been measured using the diminishing bubble method. Two different solutions have been used: (i) DMPC vesicle suspension in water obtained through sonication and (ii) DMPC dissolved in ethanol plus water mixed solvent. Both solutions contain 0.1 M NaCl. The behavior of the dynamic contact angles is very different for NBF from the two types of solutions. In the case (i) the initially constant theta(t) sharply increase after approximately 2 h of the spontaneous diminishing of the bubble, they follow the gas pressure variation in the cell and depend on the film area. On the contrary in case (ii) the theta(t) values are almost constant during the spontaneous diminishing of the bubble as well as during the gas pressure variation in the cell and they do not depend on the film area. The gas permeability coefficient is larger in case (ii). The results are discussed in connection with the thickness and structure of the NBF from the two types of solutions, taking into account the solubility (or insolubility) and the hydration of the adsorption layers of the DMPC molecules.

Phospholipid black foam films: dynamic contact angles and gas permeability of DMPC+DMPG black films.

The behavior of black foam films from aqueous dispersions of dimyristoylphosphatidyl-choline (DMPC) with addition of the soluble phospholipid dimyristoylphosphatidylglycerol (DMPG) has been studied in dynamic conditions. The dynamic contact angles theta and the gas permeability coefficient K have been measured using the diminishing bubble method. The DMPC vesicle suspension in water is obtained through sonication and DMPG is dissolved in it. Two solutions with different NaCl concentrations (0.1 M and 0.5 M) have been studied. The behavior of the dynamic contact angles is very different for DMPC black films with, and without DMPG, respectively. They follow very different time dependence during spontaneous or forced variations of the bubble size. The gas permeability coefficient is significantly reduced by the DMPG addition. The NaCl concentration also influences this specific behavior. It seems that the electrically charged DMPG anions, which determine a significant electrostatic disjoining pressure, play an important role for this specific behavior. The results are discussed in connection with data regarding the thickness and structure of these black foam films. Films from DMPC+DMPG solutions in ethanol plus water mixed solvent have been studied as well, but no quantitative results could be obtained.

The role of information for improvement of patients' treatment in Bulgaria.

PURPOSE: This issue is an attempt to assess patients' role as regards their compliance, respectively their non-compliance. The authors try to elucidate the factors concerning the patient-physician interrelation and patient-pharmacist interrelation that influence the non-compliance in order to increase the compliance rate. METHODS: Standard individual questionnaires and interviews were developed and applied to study an attitude to compliance and non-compliance among different categories of patients, suffering from chronic diseases. RESULTS: The obtained results show that the main reasons, influencing the patients' non-adherence to physicians' advise are: the high price of the drugs, the overburdened daily regimen, negligence, distrust towards the treatment and others. The insufficient information in the patient's leaflet together with the inappropriate drug form appears to be the main factors that cause non-compliance. This happens especially in the cases, when the patients are treated with more than one drug in different drug forms and particularly it concerns elderly people. Even though the compliance among the patients investigated was comparatively high (50% to 92%), possibility for improvement still exists if the treatment that have to be initiated could be individualised. Thus the level of compliance will be improved and increased. DISCUSSION: The results from the data analysis show a great variation in the level of compliance among the chronic patients in Bulgaria. It ranges from 50 to 92%, depending on the type of the chronic disease and on the age of the patients. This fact shows the necessity for improvement of the different factors that has to begin as soon as possible.

[Evaluation of initial results of treatment of lead poisoning with EDTA]. / Valutazione dei primi risultati della terapia del saturnismo con EDTA.

The results of EDTA therapy were studied in 37 workers of a battery factory consisting of males with varying degrees of occupational lead poisoning (low exposure: 10 subjects, blood lead levels (PbB) lower than 400 micrograms/l with slight alterations in heme biosynthesis; beyond limit of effect: 5 subjects, PbB > 400 micrograms/l; slight intoxication: 19 subjects, with marked alterations in heme synthesis and preclinical signs of intoxication; average degree of intoxication: 3 subjects with clinical signs of intoxication. Clinical symptoms and the following parameters were investigated: blood lead (PbB), delta-aminolevulinic acid dehydratase in erythrocytes (ALA-D), zinc protoporphyrin (PP) in erythrocytes and delta-aminolevulinic acid (ALA) in 24-hour urine before and after EDTA chelating therapy. Simultaneous measurement of ALA-D and PP showed high diagnostic sensitivity in detecting lead poisoning in occupationally exposed subjects. In view of the high interindividual variability of the results, these indices did not, however, permit a useful differentiation to be made of the different degrees of intoxication at individual level, even though a good correlation was observed between PbB and porphyrin metabolism indices. From the alterations observed in ALA-D and PP values it was not possible to establish an association between degree of alteration and types of clinical symptoms in the different intoxication studies. At the end of EDTA treatment, a clinical improvement was observed in all cases studied but only in 5 cases was a reduction in PbB observed, to levels below 1.20 mol/l, which is accepted as a permissible limit for the general population; in 17 cases PbB remained at levels above the critical value for occupational lead poisoning (400 micrograms/l), although there was a decrease after treatment. The improvement observed in the indices of porphyrin metabolism at the end of treatment was only slight: significant variations were measured only for PbB. After treatment no association was observed between ALA-D and PP variations in erythrocytes and improvement in clinical symptoms; measurement of these indices therefore seems to be of little use in assessing the efficacy of the treatment. In spite of its limited diagnostic sensitivity during intoxication, measurement of ALA in urine could be useful to assess the efficacy of chelating therapy in subjects in whom the values are initially altered.

Information needs of young scientific workers and pre-graduated students in the sphere of pharmacy.

The development of the Pharmaceutical science and its information insurance in the conditions of a transition period attain greater importance. The increase of the stream of information is more and more difficult for processing and from there-for usage.

Assessment of pharmacy patients' compliance in Bulgaria (2001--2002).

The goal of this issue is to assess the level of compliance, respectively of non-compliance among pharmacY patients between the years 2001 and 2002 in Sofia, Bulgaria. The authors study and emphasize on the factors that influence the non-compliance of the patients and also try to find different ways to increase the rate of compliance in Bulgaria. Two types of standard individual questionnaires are applied for assessment of the state of compliance and non-compliance among the pharmacy patients. The obtained results show that the main reasons, influencing the non-adherence of the patients are: the high average price of the drugs, the overload daily regimen, inattention, distrust to the treatment and others. The drug form appears to be one of the main factors that cause non-compliance, especially when the patients receive more than one drug in different drug forms few times a day and especially if elderly patients are addressed. Despite the presented comparatively high level of compliance among the patients (from 53% for 2001, to 82% for 2002), there are strategies to enhance compliance that have to be initiated. They incorporate communication tactics, patient's education, and proper dosage of the drugs and scheduling of the drug application. The results of the analysis of the received data show an increase in the level of compliance for the pharmacy patients in Bulgaria. For 2001 it was 53%, while for 2002 it has increased to 82%. This fact shows the influence of strategies for improvement of compliance.

Pharmaco-economical analysis of the treatment with antibiotics in a surgery department.

The fulfillment of a pharmaco-economical analysis of the treatment with antibiotics is an important task in the conditions of a transition period, that is currently in Bulgaria. The great problem with the insufficient financial sources prevents the supply with drugs, medical supply and technology. This analysis is a kind of an auxiliary source in the process of managing in the sphere of the health policy and in particular--in the sphere of the pharmacy.

Asthma, drug medication and noncompliance.

UNLABELLED: According to the new concepts, asthma is a chronic disease of the upper respiratory tracts, caused by different cells, including the mastocits and eozinofils. The patients that are suffering from episodic, frequent, or chronic asthma are participating very energetic in the treatment--they have to know and control the symptoms of their disease and also to possess technical skills to perform the treatment. METHODOLOGY: Between March 1 and July 31, 1999, 30 patients [19 women and 11 men, mean age 35 years (range 2.50 to 65)], followed at the Clinic for Allergic Diseases of the University hospital "Aleksandrovska", Medical University of Sofia, Bulgaria, were interviewed blindly in order to assess their compliance with pharmacologic therapy. All patients were suffering from different types of asthma. RESULTS: The level of compliance among the studied group of patients is 86%. In comparison with the literary data where the level of non-compliance is 20% the obtained level is lower--14%. The reasons for non-compliance according to the patients are: the appearance of ADRs, the high prize of the drugs, the hard application of the drug form.

Comparison of the compliance of pharmacy patients.

This issue is an attempt to be compared the compliance, respectively non-compliance among pharmacy patients between the years 1998 and 2001. The authors make an attempt to elucidate the factors that influence the non-compliance of the patients in order to improve it and to increase the rate of compliance among them. A questionnaire is applied for assessment the state of compliance and non-compliance among the pharmacy patients. The results of the analysis of the received data show that the level of compliance was 69% in 1998 and has decreased to 53% in 2001. The main reasons that influence the non-adherence of the patients are shown.

Cancer, drug medication and noncompliance.

This issue is an attempt to expose the extent of compliance, respectively of non-compliance among the oncological patients of the Central Oncological centre in Sofia. There are several factors that influence upon the degree of nonadherence. The authors make an attempt to elucidate them in order to increase the rate of compliance among this group of patients. The results of the analysis of the received data show that the level of the compliance is 92% among the studied cancerous patients. Despite the shown high level of compliance there are possibilities for the individualization of their treatment.

Low dose treatment with methotrexate-adverse drug reactions survey.

Antineoplastic drugs caused various and frequent adverse drug reactions (ADR) in connection with their pharmacodynamics. Methotrexate (MTX) ADRs are preferably gastrointestinal disorders and hepatotoxicity (hepatic enzyme abnormalities). The aim of this study was to detect and analyse ADR induced by low-dose MTX treatment in rheumatology. We observed 94 patients, 63 with rheumatoid arthritis and 31 with psoriatic arthritis. All patients were co-medicated with nonsteroidal anti-inflammatory drugs (NSAID) as Diclofenacum, Indomethacinum, Piroxicamum and 51% with glycocorticosteroides. During the follow-up study we collected 18 case-reports with ADR for 17% of the patients. From the patients with registered ADR, 11 was treated with standard dose of 7.5 mg MTX for a week and 7 patients received from 10 to 15 mg for a week. The distribution of the cases according patients' gender was 9 females and 7 males. Prevail individuals in age groups' 41-50 and over 61 years. The most frequent adverse drug reactions were leucopenia, trombocytopenia, skin reactions and gastrointestinal disorders as vomiting, melaena, epigastrial pain, etc. The primary risk connected with long therapy of low doses MTX is hepatotoxicity that diagnose and treatment are painful and expensive. As a result of the appearance of ADR in 5 patients the therapy with MTX was not changed, in two cases MTX is stopped timely or the dosage is changed and in the rest 11 patients MTX was excluded from the therapeutic scheme.