Joana I. Simeonova, Snejanka T. Tisheva-Gospodinova, Yoana M. Todorova, Petkana A. Hristova, Asia N. Yanakieva and Martin I. Hristov
Mirosław Jasiński, Magdalena Chrościńska-Krawczyk and Stanisław J. Czuczwar
Background. Adenosine is regarded as an endogenous anticonvulsant and its agonists have been proved to affect the anticonvulsant activity of a number of antiepileptic drugs (AEDs) in animal models of seizures.
Aim. To evaluate effects of adenosine agonists on carbamazepine (CBZ) and valproate (VPA) in mouse model of generalized tonic-clonic convulsions.
Methods. The following adenosine receptor agonists were used: A1 – cyclohexyladenosine, A2A – CGS 21 680, A3 – N6-benzyl-NECA and A1 (preferentially) and A2 – 2-chloroadenosine. Their possible anticonvulsant effects were studied in a threshold electroconvulsive test for maximal electroconvulsions. The protective activity of AEDs alone or in combinations with adenosine agonists was evaluated in the form of their respective ED50 values necessary to protect 50% of mice against tonic extension of the hind limbs, following maximal electroshock, delivered through ear electrodes. The specificity of interactions between AEDs and adenosine agonists was challenged with an adenosine receptor A1 and A2 antagonist, aminophylline (5 mg/kg). The effects of AEDs alone or with adenosine agonists were tested for the occurrence of adverse effects (AE) (impairment of motor coordination) in a chimney test. All combinations with an enhancement the protective activity of CBZ or VPA were verified with the free plasma or brain concentration of these AED.
Results. Adenosine receptor agonists (cycloheksyladenosine up to 4 mg/kg; CGS 21 680 – 8 mg/kg; N6-benzyl-NECA – 1 mg/kg; 2-chloroadenosine – 2 mg/kg) did not significantly affect the threshold for maximal electroconvulsions. Cycloheksyladenosine (1 mg/kg), N6-benzyl-NECA (0.5 and 1 mg/kg) and 2-chloroadenosine (1 mg/kg) potentiated the anticonvulsant activity of CBZ. Valproate’s protective action was enhanced by one adenosine agonist – cycloheksyladenosine (1 mg/kg). Only the combination of CBZ + N6-benzyl-NECA (1 mg/kg) was resistant to aminophylline (5 mg/kg). Pharmacokinetic interactions were evident in case of the combination of CBZ + N6-benzyl-NECA (1 mg/kg) and resulted in an increased free plasma concentration of this CBZ. Interestingly, total brain concentration of CBZ confirmed the pharmacokinetic interaction as regards CBZ + N6-benzyl-NECA (1 mg/kg).
Conclusion. The best profile was shown by the combination of CBZ + 2-chloroadenosine which involved no AE or a pharmacokinetic interaction. The remaining positive combinations in terms of anticonvulsant activity were associated with general profound AE and pharmacokinetic interactions in some of them.
The International Bureau for Epilepsy (IBE) Executive Committee for the term 2013–2017 began in June 2013 during the 30th International Epilepsy Congress in Montreal. From the beginning, our primary goals were to fulfil the mission of our organisation and address problems such as awareness, education, and social issues, while promoting and protecting the human rights of persons with epilepsy (PWE) and improving trans-regional equity in access to health care services, improved prevention, diagnosis and treatment and as a consequence, a reduction in the treatment gap and alleviation of stigma worldwide. By so doing, the quality of life of PWE and those who care of them will be significantly improved. In order to achieve these aims, the IBE joined forces with the International League Against Epilepsy (ILAE) and also the World Health Organisation (WHO), regional and national IBE organisations and other stakeholders.
In addition, the participation of the IBE President in many national epilepsy events worldwide has helped to promote care and human rights of PWE nationally. A major awareness event accomplished during our term in office was the launch of the International Epilepsy Day in 2015. An IBE-ILAE event celebrated the 2nd Monday in February each year at the European Parliament with the participation of many stakeholders, PWE and advocates for epilepsy MEPs.
In 2014 in order to improve access to care, treatment, appropriate treatment for PWE worldwide, particularly in developing countries, we developed our strategy plan becoming IBE’s roadmap up to 2019 and with strategic priorities to establish epilepsy as a health priority worldwide. In June 2014, in Troina, Italy, WHO, ILAE, IBE and the Global Outreach Research Task Force organised a workshop to discuss how to improve access to antiepileptic medicines in low- and middle-income countries and, as a consequence, to produce a white paper. A unique historical achievement during our term in office was the approval from WHO and subsequently from World Health Assembly (WHA) (May 26th, 2015) the Resolution on the Burden of epilepsy, and calls on United Nation Member States to implement the WHA68.20 actions and for WHO to report back in 2018. The creation by IBE/ILAE in 2016 the legal entity Epilepsy Alliance Europe has given the opportunity for both organizations to play a partnership role in many research projects aiming to reduce the epilepsy burden in Europe and worldwide.
Desislava D. Drenska and Dimitar B. Maslarov
A Transient Ischemic Attack (TIA) is a state of emergency and an independent risk factor for ischemic stroke. The social significance of the disease is determined, based on the probability of occurrence of subsequent cerebrovascular incidents and their frequency among groups. The purpose of the present study was to perform a comparative analysis of clinical features and outcome in patients with TIA for at least 24 months after onset had been registered, according to the pathogenesis and to ABCD (2) score. Two hundred and fifty-seven patients were monitored at the Neurology Clinic, First MHAT – Sofia after suffering an initial TIA. All subjects were studied using a clinical evaluation of pathogenetic mechanisms and an ABCD (2) algorithm. A diagnosis of TIA was confirmed by neuroimaging. The comparison between specific pathogenetic mechanisms demonstrated a statistically significant difference. Two TIA subgroups were involved – thromboembolic and cryptogenic (p<0.05). Also, according to the ABCD (2) score results, significant differences were found between groups at low (1-3) and high (6-7) risk, and those at intermediate (4-5) and high risk (p<0.01). Detailed investigation and assessment of patients with TIA are important concerning the prognostic outcome.
Tsvetelina V. Petkova-Marinova, Boryana K. Ruseva and Bisera D. Atanasova
Anemia is an important public health problem worldwide. Although iron (Fe) deficiency is considered the main factor in the pathogenesis of anemia, only 40-60% of anemia cases are responsive to Fe supplementation. Considerable data exist that other micronutrient deficiencies, such as selenium (Se), could be possible causes of anemia. The issue of Se deficiency as a risk factor for the development of anemia is of particular interest to our country since the Balkan region is known by a low Se content of soils. The aim of the study was to examine the contemporary conception of the influence of Se deficiency on the development of anemia by a review of the scientific literature. Most animal studies have shown a significant relation between Se deficiency and anemia, but one study indicates that there is no impact of Se deficiency on the hematological parameters. Associations of low serum Se with anemia have been found in a number of human studies including subjects of various age groups and pathological conditions. Three possible biological mechanisms have been suggested for the involvement of Se deficiency in the development of anemia: increased oxidative stress, modulation of inflammation through induction of interleukin-6, and increased expression of heme oxygenase-1. A more categorical clarification of the relationships between Se deficiency and development of anemia is needed with respect to appropriate trace element supplementation in cases of anemia with insufficient or absent therapeutic response to Fe treatment.
Stefka M. Delimitreva, Ralitsa S. Zhivkova, Irina V. Chakarova, Valentina P. Hadzhinesheva, Vladislav V. Lazarov and Dimitrina K. Dimitrova-Dikanarova
The reaction of anti-sperm antibody-positive sera from infertile women with fractionated mouse ovarian antigens was measured by enzyme-linked immunosorbent assay (ELISA). Antigens were obtained by extraction for nuclear matrix and intermediate filaments (NM-IF) producing three protein fractions – soluble, cytoskeletal and NM-IF. The results showed that sera from some infertile patients, but not control sera, react with either the soluble fraction or the NM-IF fraction. The reaction with soluble proteins was most likely directed against surface antigens, possibly aggravating the fertility problems, while the anti-NM-IF antibodies could indicate release of insoluble intracellular components by tissue damage of unknown origin.
Pencho P. Genov, Nikolay H. Kolev, Rumen P. Kotsev, Vladislav R. Dunev, Boyan A. Stoykov, Aleksander A. Vanov, Jitian A. Atanasov and Pencho T. Tonchev
Premature ejaculation (PE) is the most common sexual dysfunction in men, yet it is not well studied. Its frequency reaches 30% for men from 18 to 59 years of age in different countries. The aim of this article was to investigate the quality of sexual life in men with primary PE operated on with microsurgical penile denervation, using the Brief Male Sexual Functional Inventory (BMSFI). From September 2011 to March 2014, 22 patients were operated on with microsurgical penile denervation in the urology clinic of the University Hospital - Pleven and the Department of Urology at UMHAT Ruse AD. The mean result from the BMSFI in patients was 22 points preoperatively, indicating significant worsening of sexual function and quality of life in all five questionnaire domains. After surgery, the results increased to 28, 33 and 39 respectively, at 3, 6 and 12 months, respectively. Premature ejaculation not only leads to problems in controlling ejaculation but also worsens the overall sexual function and quality of life of patients.
Boyan A. Stoykov, Nikolay H. Kolev, Rumen P. Kotsev, Fahd Al-Shargabi, Pencho P. Genov, Aleksandar Vanov, Jitian A. Atanasov, Manish Sachdeva, Pencho T. Tonchev and Maria I. Koleva
During the last few years, prostate cancer is more frequently diagnosed in young patients. This lays emphasis on the necessity to preoperatively evaluate the sexual function in patients undergoing bilateral nerve sparing radical retropubic prostatectomy (BNSRRP). The aim of our study was to make an objective evaluation of the basic sexual function in patients with clinically localized prostate cancer and candidates for BNSRRP, using internationally validated questionnaires. We also tried to find a correlation between these questionnaires and the individual assessment of candidates, on one hand, and between comorbidities of the patients and degree of erectile dysfunction (ED), on the other hand. From January 2014 to March 2017, at the urology clinic of University Hospital – Pleven, 64 patients opted BNSRRP and reported to have preserved erectile function (EF), wishing to maintain this function after surgery. The patients’ histories and comorbidities were recorded on the day of hospitalization. The subjective assessment of the patients’ potency was compared with International Index of Erectile Function (IIEF). According to the EF domain of the IIEF, baseline EF was assessed in 28 patients. Twelve patients had mild ED, 9 patients had mild to moderate ED, seven patients had moderate, and eight had severe ED. The results showed that a significant number of patients with clinically localized prostate cancer who were candidates for BNSRRP reported to be fully potent but actually had impaired EF preoperatively. There was also a pronounced correlation between concomitant diseases and EF.
Stancho S. Stanchev, Alexandar A. Iliev, Lina G. Malinova, Boycho V. Landzhov, Georgi N. Kotov and Dimka V. Hinova-Palova
The impact of hypertension on the kidney is associated with a number of morphological changes, which gradually lead to development of end-stage kidney disease. The aim of the present study was to trace the postnatal histological changes in the morphology of nephrons and renal interstitium in spontaneously hypertensive rats. In this study, we described and compare alterations in renal histology as a consequence of hypertension in two age groups of spontaneously hypertensive rats, aged 2 and 6 months (n=3; per age group). The description of the alterations in renal morphology was made by light microscopic analysis using routine haematoxylin and eosin staining, periodic acid Schiff (PAS) reaction and Mallory’s trichrome staining. We did not observe significant changes in renal histology in 2-month-old rats: renal corpuscles were relatively well preserved, proximal and distal tubules were clearly demarcated, and no pathological changes in the larger intrarenal blood vessels were found. There was evidence of glomerular and tubular basement membranes thickening and focal interstitial fibrosis. In 6-month-old rats, we noted pronounced glomerulosclerosis, periglomerular and periarteriolar fibrosis and expansion of interstitial fibrosis. The vascular alterations depended on the size of the blood vessels and included hyaline arteriosclerosis, fibrinoid necrosis and myointimal thickening of interlobular arteries. Untreated hypertensive nephrosclerosis is associated with progressive renal alterations, which cause impaired renal function – a lifelong limiting factor.
Tihomir P. Totev, Grigor A. Gorchev, Slavcho T. Tomov, Ina D. Filipova and Nadezhda H. Hinkova
The presence of functioning endometrial glands and stroma outside the uterine cavity is defined as endometriosis. Its incidence is approximately 10-15% of women of fertile age. Incisional endometriosis following obstetric or gynecologic surgery is reported in 0.03-1.08% of women. Most of the cases reported in the literature are related to caesarean section and have required a differential diagnosis with a hernia, abscess, granuloma or lipoma. The diagnosis is based on histological findings. We describe incisional endometriosis in four patients operated on at St. Marina Hospital – Pleven for one year.