Біотехнологічні компанії у процесі консолідації фармацевтичної галузі

Evolution has provided us with a highly flexible neuroendocrine threat system which, depending on threat imminence, switches between active escape and passive freezing. Cortisol, the "stress-hormone", is thought to play an important role in both fear behaviors, but the exact mechanisms are not understood. Using pharmacological functional magnetic resonance imaging we investigated how cortisol modulates the brain's fear systems when humans are under virtual-predator attack. We show dissociated neural effects of cortisol depending on whether escape from threat is possible. During inescapable threat cortisol reduces fear-related midbrain activity, whereas in anticipation of active escape cortisol boosts activity in the frontal salience network (insula and anterior cingulate cortex), which is involved in autonomic control, visceral perception and motivated action. Our findings suggest that cortisol adjusts the human neural threat system from passive fear to active escape, which illuminates the hormone's crucial role in the adaptive flexibility of fear behaviors. Hum Brain Mapp 36:4304-4316, 2015. © 2015 Wiley Periodicals, Inc

Enhanced Fear Expression in a Psychopathological Mouse Model of Trait Anxiety: Pharmacological Interventions

The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors. Here we investigated the relationship between a genetic predisposition to trait anxiety and experience-based learned fear in a psychopathological mouse model. Male CD-1 mice selectively bred for either high (HAB), or normal (NAB) anxiety-related behaviour on the elevated plus maze were subjected to classical fear conditioning. During conditioning both mouse lines showed increased fear responses as assessed by freezing behaviour. However, 24 h later, HAB mice displayed more pronounced conditioned responses to both a contextual or cued stimulus when compared with NAB mice. Interestingly, 6 h and already 1 h after fear conditioning, freezing levels were high in HAB mice but not in NAB mice. These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line. The enhanced fear response of HAB mice was attenuated by treatment with either the α2,3,5-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429. Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias

Role of corticotropin-releasing hormone in the impact of chronic stress during pregnancy on inducing depression in male offspring mice

This is an accepted manuscript of an article published by Elsevier in Brain Research on 30/07/2020, available online: https://doi.org/10.1016/j.brainres.2020.147029 The accepted version of the publication may differ from the final published version.This work was supported by the National Natural Science Foundation of China (grant no. 81773452).Published versio

Treatment of peritoneal metastases from gastric carcinoma

Patients with advanced gastric cancer and positive peritoneal cytology and/or peritoneal dissemination are deemed to be incurable and to hold dismal prognosis. So far, the only treatment option for these patients has been palliative systemic (chemo)therapy. However, for the last three decades, great progress has been made in attempts to treat (potential) peritoneal dissemination by means of complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) after preoperative systemic therapy. This review is focused on the recent achievements of this multimodal strategy. Additionally, the review stands as background for the 4th International Conference “Advances in Surgical Oncology” that was held at the Medical University of Lublin (Poland) in November 2017, and dedicated to cytoreductive surgery and HIPEC for advanced gastric cancer

Hyperthermic intraperitoneal chemotherapy (HIPEC) in combined treatment of locally advanced and intraperitonealy disseminated gastric cancer: A retrospective cooperative Central-Eastern European study

Background and Objectives: Clinical experience in Western Europe suggests that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are promising methods in the management of gastric cancer (GC) with peritoneal metastases. However, there are almost no data on such treatment results in patient from Central‐Eastern European population. Methods: A retrospective cooperative study was performed at 6 Central‐Eastern European HIPEC centers. HIPEC was used in 117 patients for the following indications: treatment of GC with limited overt peritoneal metastases (n = 70), adjuvant setting after radical gastrectomy (n = 37) and palliative approach for elimination of severe ascites without gastrectomy (n = 10). Results: Postoperative morbidity and mortality rates were 29.1% and 5.1%, respectively. Median overall survival in the groups with therapeutic, adjuvant, and palliative indications was 12.6, 34, and 3.5 months. The only long‐term survivors occurred in the group with peritoneal cancer index (PCI) of 0‐6 points without survival difference in groups with PCI 7‐12 vs PCI 13 or more points. Conclusions: GC patients with limited peritoneal metastases can benefit from CRS + HIPEC. Hyperthermic intraperitoneal chemotherapy could be an effective method of adjuvant treatment of GC with a high risk of intraperitoneal progression. No long‐term survival may be expected after palliative approach to HIPEC