Volumen 7 (2014): Heft 1 (November 2014)

Progressive multifocal leukoencephalopathy (PML) is ademyelinating disease caused by infection with Polyomavirus hominis 2, popularly known as JC virus (JCV). The disease is usually fatal as it develops due to the progressive destruction of oligodendrocytes in multiple brain foci. Several substances that show effect against JCV have been investigated. However, only the antimalarial drug mefloquine has been reported to significantly influence the viral replication both in vitro and following in vivo therapy with good penetration and distribution of the drug at efficacious concentrations into the central nervous system (CNS). The current material presents some of the available published data, suggesting that the activity of mefloquine against JCV be considered for treatment of patients with PML.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer which is clinically negative for expression of steroid hormones and HER2 protein. According to DNA microarray profiling, breast cancer was divided into several molecular subgroups, including Luminal A and Luminal B; HER2 overexpressing; normal breast- like and basal-like subtype. TNBC comprises tumours that express heterogeneous molecular and immunohistochemical phenotype, thus determining different prognosis. The majority of TNBC carry the “basal-like” molecular profile on gene expression arrays. Basal-like carcinomas of the breast associated with poor prognosis often correlate with expression of Caveolin-1. The study aimed to investigate the expression of caveolin-1 in the tumour cells and in the stromal component of the tumour among the group of TNBC and compare it to the expression of caveolin-1 in a control group with non-TN breast cancer. Whole tissue sections were used. Formalin fixed, paraffin embedded tissue materials from 101 patients diagnosed with invasive breast cancer during the period 2004-2007 were investigated in a retrospective study. A multistep approach was used to separate the different subtypes of breast cancer. During the first step the breast tumours were separated according to their ER, PgR, HER 2 and proliferative activity, using the Ki-67 index. The triple- negative tumours were additionally tested for EGFR and CK5/6. The basal breast cancer group was finally subdivided into basal and baso-luminal according to the type of expression of basal cytokeratins. caveolin-1 expression was examined in the tumour parenchyma and stroma. According to our results, caveolin-1 expression in breast cancer was significantly associated with basal biomarkers expression (basal and baso-luminal type of BC) χ²= 33.4; p<0.0001. Caveolin-1 can be used as a potential marker to examine the presence of basal phenotype in breast cancer.

The aim of the study was to present our own experimental model of blunt chest trauma in small laboratory animals. Fifteen Wistar albino rats (body weight 290.0-320.0 g) were used in the experiment. An originally designed platform was used to inflict blunt thoracic trauma in the rats. Gross examination and histological evaluation of the heart and lung were performed. It was established that blunt chest trauma caused three thoracic injuries: bilateral lung contusion, myocardial contusion and hemopericardium. These thoracic injuries occurred as a result from direct compression of the chest wall towards the lung and the heart. The severity of lung parenchymal and myocardial pathological findings depended on the energy of blunt chest trauma. The study presents a reproducible small-animal experimental model of blunt chest trauma. The model gives opportunities for further studying different aspects of lung and myocardial contusion.

Leptin inhibits feeding, reduces body weight and increases thermogenesis. Experimental data suggest involvement of GABAergic mechanisms in the regulation of feeding behavior and energy balance. The present study was set to determine the effect of combinations from leptin, GABA_B-agonist baclofen and GABA_B-antagonist CGP35348 on thermoregulation of male Wistar rats, using in vivo and in vitro experiments. The substances used for in vivo experiments were administered intraperitoneally (i.p.). The measurement of the body temperature was done via thermistor probes (TX8) and monitored on multichannel recorder Iso-Thermex16. In vitro experiments were conducted on rat PO/AH neurons, recorded extracellulary by conventional electrophysiological equipment, using brain slice preparations. The separate intraperitoneal injection of leptin as well as GABA_B-antagonist CGP35348 produced significant hyperthermia in rats while the GABAB-agonist baclofen caused a decrease in the core body temperature. The probable synergy between the hyperthermic effects of leptin and GABA_B-antagonist did not occur. On the contrary, the effect of this combination was lower as compared to the result of the separate administration of GABA_B-antagonist. When leptin was applied just prior to GABA_B-agonist baclofen, neither of their separate effects appeared. In vivo effects determined correlated with in vitro changes of firing rate observed in PO/AH neurons. The data from this study provide a new point of view concerning the interactions of leptin and GABA on the level of thermoregulation. These results represent a step forward in understanding the complicated mechanisms involved in thermoregulation.

The aim of the study was to explore the impact of oxidative stress on frozen seminal plasma in fertile and infertile men by examining the total antioxidant capacity. Patients: Infertile patients from male infertility clinic with various diagnoses and fertile men. Design: Seminal plasma from proven fertile men [n=50] and infertile patients [n=50] were examined for total antioxidant capacity (TAC) level, semen parameters such as morphology, motility and concentration, and DNA integrity test. Interventions: Seminal plasma TAC measurement by luminometric assay using the TAC assay kit, semen analysis parameters, DNA integrity test. Fertile men showed higher TAC values (median and SD): 1201µM (SD±548), as compared with the infertile patients: 831μM (SD±343). The result from sperm morphology of fertile patients showed a mean percentage of 4.8 % (SD±1.68) whereas the percentage in the infertile group was 2.68% (SD ±1.68). The same group of samples, analyzed for DNA damage showed a mean of DFI 10.38% (SD±5.17%) in fertile men and a mean of DFI 17.22% (SD±7.22%) in infertile men. Total antioxidant capacity of the seminal plasma as measured by the luminоmetric assay is a reliable and simple test for diagnosing and management of male infertility.

The aim of this study was to identify family factors determining risk sexual behavior among students aged 12- 18 in Veliko Turnovo region. A cross-sectional study was conducted in 2014. Three hundred and ten students were included in a representative sample of students attending seven schools in Veliko Turnovo region. The respondents filled in a self-administered questionnaire, designed to collect data on family interactions, acts of sexual coercion, parental social status and their influence on the sexual behavior of the students. Data were processed using SPSS.v.19. Parametric and non-parametric statistical methods were applied. About one-fifth of the students were nurtured in incomplete families. History of a sexually transmitted diseases correlated with type of family (p<0.05). Poorer family interactions (rare family dinners and no conversations about sex) determined acts of risk sexual behavior - accidental contraceptive use during sex and postponing an obstetric examination (p<0.05). Students reporting sexual coercion had also had frequent casual sexual intercourse (p<0.05). Identifying family factors is of essential importance in planning effective sexual health education at school.

To assess the changes in the serum concentrations of 25(ОH)D in relapse and remission and their relation to the degree of neurological deficit. We analyzed 53 subjects (30 controls and 23 patients) from October 2012 to Маy 2013. Diagnosis was based on McDonald 2010 criteria. The severity of neurological deficit was assessed by the Expanded Disability Status Scale. Serum concentrations of 25(ОH)D (nmol/l) were measured by ELISA once in controls and twice in patients - in relapse and remission. Mean levels in all groups were in the mild to moderate deficiency range, being lowest in the patients in relapse (controls 31.46±7.3; relapse 26.93±7.44; remission 28.06±7.28). There was a trend for lower levels of 25(ОH)D in healthy females in comparison to their male counterparts, and in female patients in relapse as compared to males (female controls - 26.56±8.4, male controls - 41.35±11.86; females in relapse - 26.33±10.03, males in relapse - 28.06±11.08). Negative statistically significant correlations between the concentrations of 25(ОH)D during relapse and remission and the degree of neurological deficit in the corresponding period were found (cc. -0.593, Sig 0.03, relapse; -0.46, Sig 0.024, remission). Assessment of the risk for development of MS, regarding the 25(ОH)D showed protective effect with respect to the risk of disease occurrence (ОR: 04125 relapse; 0.578 remission).

The aim of the study was to identify socioeconomic and psychological determinants of self-rated health among ambulatory and hospitalized patients. A cross-sectional study was carried-out in 2014. Two hundred and twelve patients over 44 years of age filled in a self-administrated questionnaire. Self-rated health (SRH) was measured by 5-point range scale. The level of well-being (WB), sources of social support, personal financial capacity, social status, etc. were studied as well. Data were processed by SPSS.v.19. Parametric and non-parametric statistical methods were applied. Over 70% of patients evaluated their health as fair and good. The persons with higher WB had higher SRH, that correlation was moderate (r=0.452; p=0.001). In regard to the social status the differences were significant - the unemployed, old age retirees or ill health retirees evaluated their health lower (p<0.05). A proportion of patients indicated two or more sources of emotional and instrumental support, but increased number of support sources had no effect on SRH (p>0.05). Identification of socioeconomic and psychological factors of self-rated health allows clarifying better their effect mechanisms and planning appropriate health services

Angiomyolipomas are benign mesenchymal neoplasms, presenting with a variable mixture of adipose tissue, smooth muscle and vascular component. Although they are typically found in the kidneys, many cases of extrarenal angiomyolipomas have been reported. They are extremely rarely present in the uterus. We describe a case of a 56-year-old woman, operated on for leiomyoma. Total laparohysterectomy and bilateral adnexectomy was performed. After histological and immunohistochemical examination, the final diagnosis of uterine angiomyolipoma was made. Renal and extrarenal angiomyolipomas are compared in regard to clinical and morphological aspect and their difference from PEComas is dicussed. PEComas have been defined during the last decade and there are still issues regarding terminological clarity and overlapping.

Tropical fresh water stingrays have become quite popular among amateur and professional aquarists due to their attractive appearance. However, the species may have a high life-threatening potential. Stingray intoxication is rare in Eastern Europe and there is no specific antivenin available. We present the first case of “rayism” - envenomation caused by sp. Reticulatus in Eastern Europe. The patient was a 63-year-old amateur aquarist, with a history of ischaemic heart disease and allergy to NSAIDs. He got stung while cleaning a stingray fish tank and was admitted to the department of clinical toxicology 40min following the incident, with symptoms of moderate intoxication: accentuated local toxic syndrome - mild bleeding at the sting site, worsening and excruciating (8- 9/10) pain in his left hand and forearm, feeling of “burning” in the arm, accompanying toxic symptoms - vertigo, malaise, fatigue, sweating and tightness in the chest. No antitoxin was available and the treatment plan included local aseptic treatment of the wound, anti- tetanus prophylaxis, fluoroquinolone-type antibiotic prophylaxis, antihistamine, a corticosteroid and i.v. infusions. Thermal therapy (immersing the arm in hot, 45℃ tap water) completely reduced the pain within 5 hours. Full recovery was achieved on the 3^rd day after the exposure. A toxicologist should react adequately in the setting of a rare intoxication even when a specific antidote is not available. Thermal therapy proved to be effective in the case of stingray envenomation.

Fibromatoses are a group of benign proliferations of fibrous tissue with clinical behaviour ranging from that of truly malignant tumours to that of benign reactive fibrous proliferations. Some of the superficial fibromatoses are fairly common but deep ones, also known as desmoid tumours or musculoaponeurotic fibromatoses, are rare. We describe a case of extra-abdominal musculo- aponeurotic fibromatosis in a 22-years old male. He underwent 14 operations for a period of 9 years for fibromatosis of the posterior surface of the right lower limb. The histological findings of the lesions were similar consistent across surgeries and consistent with a diagnosis of aggressive extra-abdominal fibromatosis.

Methotrexate (MTX) is a cytostatic agent used in oncology. Because of its immunosuppressive properties, MTX is also used in autoimmune disorders. Low-dose MTX regimens in the treatment of rheumatoid arthritis and severe psoriasis are considered to be safe. However, pharmacovigilance centers warn of serious and even fatal incidents due to errors in oral MTX administration. The aim of this case series presentation was to identify the specific factors related to the development of adverse drug reactions (ADRs) induced by MTX. A prospective pharmacovigilance study was conducted at the Clinic of Dermatology, University Hospital, Stara Zagora. We report 3 cases of patients with psoriasis vulgaris in which severe haematological abnormalities associated with previous administration of MTX were detected during hospitalization. A 73-year old female with malaise, vomiting and oral ulcers who had taken approximately 120 mg MTX was found to have pancytopenia. A 59-year old male hospitalized for psoriatic erythroderma who had erroneously taken 10 mg MTX daily instead of weekly for 8 days, was diagnosed with bicytopenia and toxic hepatitis. An 88-year old male with psoriatic arthritis presented with aphthous stomatitis, erosive crusted lesions, ecchymoses and aplastic anemia 2 weeks after treatment with 12.5 mg MTX once weekly plus i.m. Movalis^®, followed by Diclophenac Duo^®. The main predisposing factors for the development of these ADRs were patient-related dosage errors and concomitant administration of NSAIDs. Safe use of oral MTX requires clear dosing instructions and strict patient compliance. Potential drug interactions of MTX with other drugs should also be considered.