U. Müller(1), J. Winkler(1), H.-J. Seyfarth(1), U.-F. Haustein(2), J. Schauer(1) and P. Nenoff(2,3)
(1)Department of Internal Medicine, University of Leipzig, Germany
(2)Department of Dermatology, Venereology and Allergology, University of Leipzig, Germany
(3)Laboratory for Medical Microbiology, Mölbis, Germany
Summary. The question of this in vitro study was to find out whether it might be possible to change the physicochemical properties of antifungal solutions to increase their antifungal effectiveness for local application via inhalation or intrabronchial instillation. The in vitro susceptibility of different Aspergillus species to amphotericin B, liposomal encapsuled amphotericin B, itraconazole, 5-flucytosine, and terbinafine, using different solvents (sterile water, 0.9% saline, and tyloxapol) was investigated by agar diffusion (AD) and microdilution method (MD). Using tyloxapol instead of sterile water to dissolve amphotericin B or liposomal encapsuled amphotericin B, the AD produced a significant increase of inhibition zone, whereas MD showed a decrease of minimum inhibitory concentrations. All but one Aspergillus strain exhibited a good susceptibility to polyene antifungals. 5-flucytosine showed an intermediate susceptibility. Itraconazole and terbinafine had a better effectiveness against “Non-fumigatus” – strains then against Aspergillus fumigatus. It is concluded that by combination with hyperosmolaric tyloxapol it is possible to reach isoosmolaric conditions in the solution of normally hypoosmolaric polyene antifungals. A good in vitro antifungal efficacy of the combination of polyenes with tyloxapol could be demonstrated.
Key words: aspergillus, in vitro susceptibility, antifungal drugs, microdilution, agar diffusion


L. Daliento and L. Dal Bianco
Chair of Cardiology, University of Padua, Italy


J. Radenkova-Saeva
Clinic of Toxicology, MHATEM “N. I. Pirogov” – Sofia, Bulgaria
Summary. Aim was to describe the clinical and epidemiological characteristics of life-threatening anaphylactic reactions in adults, admitted to a Toxicology Clinic, Emergency Hospital “N. I. Pirogov” in one-year period. A retrospective analysis of all patients admitted to the Clinic of Toxicology, Emergency Hospital “N. I. Pirogov“ during 2006 with life-threatening anaphylactic reactions was performed. The following criteria were used in order to obtain a complete description: patient’s age, gender, etiologic trigger, and symptom severity. 75 patients between 19 and 81 years with life-threatening anaphylactic reactions were admitted to the Department for adults in the clinic during the study period. There were 38 man (50.6%) and 37 women (49.3%). An anaphylactic shock was observed in 52% of the patients (39 cases). The other 36 (48%) of them had respiratory, cardiovascular, gastrointestinal, neurologic involvement, generalized symptoms such as diaphoresis, tingling, or an impending sense of doom, manifested with different severity. The patients had dermatologic symptoms, including urticaria, flush, warmth or angioedema. The etiologic triggers were the following: drugs – 22 cases (29.3%), insect bites – 21 cases (28%), food – 10 cases (13.3%) unknown etiology – 22 cases (29.3%). The drugs most often associated with anaphylactic and adverse reactions were: antibiotics – 8 cases, analgetics, antipyretics, non-steroidal anti-inflammatory drugs – 7 cases, others – 7 cases. Food as trigger involved tree nuts, seafood, eggs. 33% of hospitalized people have had previous allergic disease. There were not registered any lethal cases during investigated period. The results of the study revealed no differences between genders. All age groups were affected. Drugs and insect bites were among the most frequent causes for life-threatening anaphylactic reactions.
Key words: life-threatening anaphylactic reactions, anaphylactic shock, urticaria, angioedema, insect bites


A. Stoimenova(1) and F. Ribarova(2)
(1)Faculty of Pharmacy, Department of Social Pharmacy, Medical University – Sofia
(2)Faculty of Public Health, Department of Preventive Medicine, Medical University – Sofia
Summary. The nutrition during pregnancy and lactation is a critical and vulnerable point. Dietary micronutrients play an important role for mother and infant health. The aim of the article is to review the current literature on necessity of micronutrient supplementation during pregnancy and lactation. Thirty six references focused on food supplementation of pregnant and lactating women have been reviewed and assessed using MEDLINE/PubMed, Scopus database and Internet-based search for a period of the last 10 years. Daily intake of 400 μg of folic acid from fortified foods and/or dietary supplements is recommended for pregnant women (until the third trimester of the pregnancy). The use of vitamin D supplementation in the early pregnancy could prevent from preeclampsia and promote the neotanal well-being. Iron supplementation has to be managed according to the individual physiological needs. The iodine supplementation is particularly important for areas with endemic goiter. The policy makers and health specialists should identify and recognise the special needs of pregnant and lactating women, align nutritional support to meet their requirements and to ensure optimal nutrient balance.
Key words: pregnancy, lactation, dietary micronutrients

G. Petrova, A. Stoimenova and M. Dimitrova
Faculty of pharmacy, Medical University – Sofia
Sumarry. Infection with HIV retrovirus leads to AIDS and after 14 years approximately 70% of the HIV infected patients fall ill with AIDS. Economic burden of HIV is tremendous for the society and for the families because lots of new medicines are authorised with high effectiveness as well as high prices. Recently on the Bulgarian market, tenofovir for highly active antiretroviral therapy as the first nucleoside inhibitor of reverse transcriptase was authorized for sale. The goal of our study is to evaluate the cost/effectiveness of tenofovir for HIV therapy as part of the combination pharmacotherapy from the point of view of Bulgarian positive drug list for one-year period. We analysed 5 safety, efficacy and 4 pharmacoeconomic studies selected from PubMed, NICE, Cochrain library, and HTA databases as a sources for health care results information. The cost of pharmacotherapy was calculated for 6 competing HAAT. The cost-effectiveness ratio was calculated for the competing therapies. The choice of the highly active, combination antiretroviral therapy should be careful evaluated from the point of view of the cost, therapeutic results, safety profile and cost/effectiveness ratio for every particular case.
Key words: pharmacoeconomics, cost-effectiveness, HIV, highly active antiretroviral therapies

M. Lubomirova(1), A. Tzontcheva(2), J. Petrova(3) and B. Kiperova(1)
(1)Clinic of Nephrology, University Hospital “Alexandrovska” – Sofia,
(2)Department of Clinical Laboratory, University Hospital “Alexandrovska” – Sofia
(3)Clinic of Neurology, University Hospital “Alexandrovska”
Summary. Since total homocysteine (Hcy) is markedly elevated in patients with chronic renal failure (CRF), it has been presented as potential factor contributing to the high risk of cardiovascular disease in CRF. The aim of the study was to examine the significance of elevated Hcy and other cardiovascular risk factors for carotid atherosclerosis in patients with CRF. 56 patients 16-M, 40-F, average age 58±14,55, creatinine clearance 39,19±10,11 ml/min were examined. In addition, 20 healthy subjects were examined as controls. The association of Hcy levels and classic risk factors for atherosclerosis with common carotid intima- media thickness (IMT) was investigated. Hcy is markedly elevated in patients with CRF. Renal function, defined by creatinine clearance was strongest determinant for Hcy levels (r = -0,332, p<0,008). Increased IMT was estimated in pts. with CRF, compared to healthy controls (0,74±0,10 vs 0,59±0,10, p<0,001). Significant predictors for carotid IMT were: age, duration of hypertension, diabetes, (r = 0,349, p<0,05). A negative corralation between IMT and clreatinine clearance was found out (r = -0,312, p<0,004). We found association between Hcy and carotid IMT (r = 0,344, p<0,015). No consistent association was found between IMT and other specific for CRF cardiovascular risk factors. The study suggests that patients with mild renal failure have increased IMT of the common carotid artery. The elevated plasma Hcy level in CRF is associated with carotid intima-media thickening.
Key words: total homocysteine, chronic renal failure, intima-media thickness, carotid atherosclerosis

F. Ribarova
Faculty of Public Health, Medical University – Sofia
Summary. For several decades, the role of vitamin D was connected with Ca(2+) and phosphate homeostasis and with bone formation and maintenance. Now it has become increasingly apparent that vitamin D also has other very important functions, not primarily related to mineral metabolism (SCF, 2002). Many epidemiological studies, laboratory and animal investigations demonstrated that vitamin D can reduce inflammation in a variety of medical problems (Hayes, 2000; Ylikomi et al., 2002; Garcion et al., 2002); may be protective against some cancers (Blutt and Weigel, 1999; Brawley and Parnes, 2000; Campbell et al, 2000; Feldman et al., 2000); and has neuroprotective effects (Prufer et al., 1999; Baas et al., 2000; Langub et al., 2001; Trouillas et al., 2001). Macronutrient malnutrition is a current widespread problem with serious health and economic implications. Dietary surveys indicate that fortified foods and food supplements play an important role in mitigating the risk of vitamin D insufficiency associated with its critical role in a number of cellular functions.The aim of this article is to focus recent advances in the medical science on physiological importance of vitamin D and on some essential nutritional aspects.
Key words:  vitamin D functions, medical problems, physiological importance


G. Draganov, P. Peikov and D. Obreshkova
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University – Sofia
Summary. Amino acids are broadly used and included in food supplements alone or in combinations. Among them, L-tyrosine is one of the most exploited and used due to its multifunctional health benefits. L-tyrosine is a nonessential amino acid that is synthesized in the body from the essential amino acid L-phenylalanine or is directly obtained by food. Furthermore, it is a precursor in the biosynthesis of catecholamines, thyroid hormones and melanin. Preliminary evidence suggests that L-tyrosine supplementation may be of benefit in the additional treatment of depression, phenylketonuria, drug abuse and withdrawal and vitiligo. The aim of the present study is to analyze to which extent the health claims are reasonable by producers of proclaimed food supplements containing L-tyrosine on the basis of already described reviews in literature as well methods of analysis of catecholamines in biological media. In addition, analysis of the safety when high doses of L-tyrosine are administered, possible interactions with drugs, foods and food supplements on the basis of described references were also within the scope of this study. Finally, the optimum conditions for the administration of food supplements containing L-tyrosine and rationale combinations with other ingredients with the aim to enhance the effect were also investigated. A number of studies have found L-tyrosine to be useful during conditions of stress, cold, fatigue, prolonged work and sleep deprivation with reductions in stress hormone levels as well as to improve the cognitive and physical performance. The simultaneous supplementation with L-tyrosine could lead to certain risks like drug interactions or/and other adverse reactions. The present research confirms the statement that the application of food supplements containing L-tyrosine could be favorable for the health but physicians, pharmacists and other health care professionals could warn about the way of administration and also for any adverse reactions and detrimental effects.
Key words: L-tyrosine, food supplements, catecholamines



P. Peikov, D. Obreshkova and G. Draganov
Department of Pharmaceutical chemistry, Faculty of Pharmacy, Medical University – Sofia
Summary. Amino acids are broadly used and included in food supplements alone or in combinations. Among various food supplements, L-tryptophan and 5-hydroxytryptophan are some of the most exploited and used due to their multifunctional pharmacological properties. L-tryptophan is an essential amino acid in the human diet as well as it is a precursor in the biosynthesis of 5-hydroxytryptophan, serotonin, melatonin and niacin. The aim of the present study is to analyze to which extent the claims, described on the labels are reasonable by producers of proclaimed food supplements containing L-tryptophan and 5-hydroxytryptophan on the basis of information for 26 food supplements available in the Bulgarian marketplace, 108 food supplements available in the USA marketplace and already described reviews in literature. In addition, analysis of the risks when high doses of food supplements containing L-tryptophan and 5-hydroxytryptophan are administered, possible interactions with drugs, foods and other supplements on the basis of described references, case reports, FDA reports were also within the scope of this study. Finally, the optimum conditions for the administration of food supplements containing L-tryptophan and 5-hydroxytryptophan and the rational combinations with other ingredients with the aim to enhance the effect were also investigated. Physicians, pharmacists and other health care professionals could warn about the way of administration and also for the adverse reactions and detrimental effects of food supplements, containing L-tryptophan and 5-hydroxytryptophan. The health care professionals should follow the daily intake of essential amino acids including L-tryptophan obtained by food. The patients should also inform their general practitioner or pharmacist in case they administer such supplements.
Key words: L-tryptophan, 5-hydroxytryptophan, food supplements



G. Tchernev(1) and P. Nenoff(2)
(1)Department of Dermatology, Venereology and Dermatologic Surgery,
MVZ Kirchheim GmbH/VOP, Kirchheim/Teck, Germany
(2)Laboratory for Medical Microbilogy, Mölbis, Germany
Summary. A number of clinically diverse, poorly understood, and relatively uncommon skin diseases are linked together by the presence of a pattern of common histopathological elements that traditionally has been referred histologically as the “lichenoid tissue reaction” or clinically to lichenoid-like pathologies of the skin. These elements include a pattern of epidermal basal cell morphological change that has been described as “hydropic” or “liquefactive”. The chronological course of these diseases, known in the literature as Lichenoid like pathologies or Lichen ruber planus (LRP), varies. In the most LRP or Lichenoid like pathologies of the skin und oral/genital mucosa, the targeted antigen is unknown, with cross-reactivity between environmental antigens (for example, viral, drug, chemical, tumor) and self antigens been suspected. The two events, known as antigen mimicry and epitope spreading could be the possible pathogenic trigger in lichenoid dermatoses, as well as the cause of their transition into other rare forms. It is an interesting hypothesis that viral infections are probably able to initiate antigenic mimicry using different mechanisms: 1) causing reversible or irreversible disorders in the tissue homeostasis, consequently leading to a crossed immunologic reaction affecting both skin and subcutaneous area; 2) initiating directly a crossed immunologic reaction to the viral agent itself, without presenting any alterations in the tissue homeostasis, or 3) by tumorly initiated antigenic mimicry, which in most of the cases is irreversible and, generally, the prognosis regarding the affected patients is negative. A detailed study of the above mentioned items should indisputably lead to more precise diagnoses of lichenoid dermatoses and to the improvement of the life of some patients groups. It could be supposed that the early dermatologic prevention and screening programs applied to patients suffering from lichenoid dermatoses shall contribute much more to patient’s health than the determination of the immunologic cascades in blood and/or apoptotic markers in the lesional skin. The last both of them should be defined as a consequence or the final result of the antigenic mimicry or epitope spreading, and not as a direct reason of lichenoid diseases. The manuscript analyzes important new hypotheses regarding the pathogenesis of LRP which in the close future have to be analyzed in details.
Key words: lichen ruber, apoptotic pathways, ICAM-1, antigen mimicry, Fas L, epitope spreading

  © 2009