Anesthetized guinea pig as a model for drug testing.

Based on the World Health Organization statistics, cardiovascular diseases represent the major cause of death worldwide. Although a wide range of treatment approaches and pharmaceuticals is available, the therapy is often not effective enough and therefore health risks for the patient persist. Thus, it is still essential to test new drug candidates for the treatment of various pathophysiological conditions related to cardiovascular system. In vivo models represent indispensable part of preclinical testing of such substances. Anesthetized guinea pig as a whole-body model allows to evaluate complex reactions of cardiovascular system to tested substance. Moreover, action potential of guinea pig cardiomyocyte is quite comparable to that of human. Hence, the results from this model are then quite well translatable to clinical medicine. Aim of this paper was to summarize the methodology of this model, including its advantages and/or limitations and risks, based on the effects of two substances with adrenergic activity on the ECG parameters. The model of anesthetized guinea pig proved to be valuable and suitable for testing of drugs with cardiovascular effects.

Mineral water Vincentka and its influence on mucosal ulcers.

Gastropathy is one of the most common diseases of the human gastrointestinal tract. Apart from its consequences in the stomach, it is also manifested in other parts of the digestive tract, particularly in the duodenum. The aim of this pilot study was to verify on animal model the empirically observed alleviation of gastropathy symptoms in patients who underwent a drinking treatment of Vincentka natural mineral water during their spa treatment. Sixteen male Wistar rats were included in the study. The animals were randomly divided into two groups: experimental group (E; n=8) and control group (C; n=8). The experimental protocol consisted of three phases: (1) handling phase (7 days); (2) mineral water (E)/tap water (C) administration (7 days); (3) acute gastritis induction (1 day). Twenty-four hours after the induction of acute gastritis, the animals were sacrificed. The collected tissues (stomach and duodenum) and blood were examined by standard histological microscopy, and by immunohistochemical and biochemical methods. Histopathological analysis revealed significantly reduced damage to the gastric mucosa in the experimental group. Significantly different values of blood plasma antioxidant capacity, oxidative stress parameters and blood plasma biochemical parameters were also found. Based on these results, we conclude that the mineral water Vincentka has a positive impact on development and symptoms of acute gastric ulcers.

Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.

Blood vessels in the central nervous system (CNS) develop unique features, but the contribution of CNS neurons to regulating those features is not fully understood. We report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevents invasion of endothelial cells into the deep layers of the retina and causes blood-retinal-barrier (BRB) dysfunction in mice. Vascular endothelial growth factor (VEGF), which drives angiogenesis, and Norrin, a Wnt ligand that induces BRB properties, are decreased after activity blockade. Exogenous VEGF restores vessel growth but not BRB function, whereas stabilizing beta-catenin in endothelial cells rescues BRB dysfunction but not vessel formation. We further identify that inhibiting cholinergic activity reduces angiogenesis during oxygen-induced retinopathy. Our findings demonstrate that neural activity lies upstream of VEGF and Norrin, coordinating angiogenesis and BRB formation. Neural activity originating from specific neural circuits may be a general mechanism for driving regional angiogenesis and barrier formation across CNS development.

Incidence of uterine sarcomas in West Bohemia, at the Department of Gynaecology and Obstetrics, University Hospital in Pilsen, Czech Republic.

OBJECTIVE AND SETTING: A retrospective review of women of the West Bohemian population was performed at the Department of Gynaecology and Obstetrics, University Hospital in Pilsen, Czech Republic from 1/2005 - 1/2017. METHODS: The following data was analysed: patients age, histological type, tumour size, FIGO stage, body mass index, previous irradiation, Tamoxifen usage, and other possible risk factors. A total number of 20 uterine sarcoma patients were detected in the period from 1/2005 to 1/2015, and these cases were followed until 1/2017. RESULTS: The histological types identified were: leiomyosarcoma in 12 cases, endometrial stromal sarcoma in 7 cases and one case of high-grade undifferentiated uterine sarcoma. This only patient diagnosed with high-grade undifferentiated uterine sarcoma showed distant metastases 12 months after the surgical treat-ment and died one month later. The whole group of uterine sarcoma patients regardless histological subtype reached two years in 50% of cases, with the median disease-free interval 18 months and the median follow up of 38 months. The diagnosis of sarcoma was already known in 25% of cases from dilatation and curettage histology. There were suspicious sonographic findings suggestive of sarcoma in 10% of cases. Multiparity was associated with 48.2% of endometrial stromal sarcoma cases. The leading clinical symptom was postmenopausal bleeding in 55% of patients. CONCLUSION: We confirmed uterine sarcomas to be rare malignancies, even in the Czech population with high uterine malignancy incidence. Uterine cold knife morcellation during the vaginal part of laparoscopically assisted vaginal hysterectomy didnt worsen the prognosis of our patients.

[Detection of cancer stem cells in ovarian cancer]. / Detekce nádorových kmenových bunek karcinomu ovaria.

OBJECTIVE: Detection of cancer stem cells (CSCs) in ovarian cancer, influence of CSCs on overall survival, disease free interval. Results in comparison with literature. DESIGN: Original study. SETTINGS: Department of Gynaecology and Obstetrics, Faculty Hospital Pilsen and Medical Faculty in Pilsen, Charles University, Sikls Institute of Pathology, Faculty Hospital Pilsen and Medical Faculty in Pilsen, Charles University. METHODS: 23 specimens of papillary-serous ovarian carcinoma and 4 specimens of endometroid ovarian carcinoma were included in the study. Specific antibodies to CD44 and CD133 antigens were used. Immunoreaction of both CD44 and CD133 was evaluated for the high power field. RESULTS: There was no significant correlation between CD44 expression and disease free interval and overall survival. CD133 expression was not evaluated due to an inadequate immunoreaction antibody - antigene. CONCLUSION: We did not find any statistically correlation between CD44 expression and overall survival and disease free interval in our series of patients with ovarian carcinoma. It seems to be better to use different antibody for CD133 detection.