Malignant infarction in cats following prolonged middle cerebral artery occlusion : volumes of severe blood flow reduction predict fatal outcome

Severity and duration of cerebral blood flow (CBF) reduction are main determinants of injury in core and penumbra zones of focal brain ischemia. To study the putative role and predictive significance of the volume of these zones for induction of a malignant course due to edema formation in large hemispheric stroke, we examined reduction of CBF and oxygen metabolism (CMRO2) by sequential positron emission tomography (PET) in a transient ischemia model in cats that is susceptible to secondary deterioration after reperfusion.peer-reviewe

Glutamate and purine catabolites in relation to free radical production during focal ischemia-reperfusion : an in vivo study in cats

The in-vivo interrelation between excitotoxicity and oxidative stress following cerebral ischemia in cats was investigated. To elucidate the role of this mechanism in cerebral ischemia, the study presented herein sought to investigate the spatial and temporal features of the free radical response to elevations of glutamate and purine catabolites in a reproducible model of in vivo focal ischemia/reperfusion. The time course of neurochemical and Reactive Oxygen Species (ROS) were simultaneously conducted in ischemic focus and perifocal region of the brain.peer-reviewe

Extracellular glutamate accumulates only in final, ischemic stage of progressive epidural mass lesion in cats

Epidural mass lesions may cause ischemia due to progressive intracranial hypertension. In order to 1) investigate the impact of intracranial pressure (ICP) on accumulation of neuroactive substances, and 2) test the significance of neurochemical monitoring for early prediction of fatal outcome, we gradually raised ICP in cats by inflation of an epidural balloon: We assessed extracellular substrate alterations in the contralateral cortex in relation to changes of ICP, cerebral perfusion pressure (CPP) and mean arterial blood pressure (MABP). In a complementary experiment, regional cerebral blood flow was assessed by sequential positron emission tomography (PET).peer-reviewe

The compelling arguments for the need of medical vascular physicians in Europe

<b></b> The burden of vascular diseases is growing worldwide, as the population ages, prompting a call to action not only in terms of awareness but also and most urgently in recognizing the need for vascular physicians, also called angiologists. Vascular medicine views the vascular system (arteries, veins, and lymphatics) as a whole, unique, and independent entity requiring specialized competencies. Vascular physicians offer a holistic and comprehensive approach to vascular patients including provision of interventional procedures, management of a heterogeneous group of multi-morbid and frail patients affected by multi-vessel diseases, and connecting different specialists in a multidisciplinary effort. Vascular medicine practise varies across European countries. While it is a firmly accepted medical speciality in many European countries it is not formally recognized by the European Union limiting adoption in the other countries. The lack of vascular physicians likely accounts for inequality of care of vascular patients as compared for example to patients with heart disease and might contribute to adverse outcomes and healthcare costs associated with vascular diseases. To move forward in the struggle to provide efficient care for multimorbid poly-vascular patients, it is essential to establish vascular medicine programs in Europe and worldwide. Important steps to achieve this goal include improving public awareness of vascular diseases, attain formal recognition by the EU of angiology/vascular medicine as a medical specialty, creating specialized treatment guidelines, and to harmonize vascular care in Europe

ИСТОРИЯ ІІ МИРОВОЙ: МЕЖДУ СКИЛЛОЙ РЕВИЗИОНИЗМА И ХАРИБДОЙ СТЕРЕОТИПОВ, В ПЛЕНУ АКТУАЛЬНОСТИ

В статті аналізується висвітлення в сучасній історіографії пострадянських країн низки проблемісторії ІІСвітової війни, насамперед концепції ревізіоністського характеру, та дається оцінка їхньої обґрунтованості.This article analyzes coverage of contemporary historiography of post-Soviet countries, a number of problems in the history ofWorldWar II, especially the concept of a revisionist nature, and assesses their validity

Immunotherapy of Peritoneal Carcinomatosis with the Antibody Catumaxomab in Colon, Gastric, or Pancreatic Cancer: An Open-Label, Multicenter, Phase I/II Trial

Background: Peritoneal carcinomatosis (PC) is common in gastrointestinal (GI) cancer and there is no effective standard treatment. We investigated the tolerability and maximum tolerated dose (MTD) of the trifunctional antibody catumaxomab in patients with PC. Methods: In this open-label, phase I/II clinical trial, patients with epithelial cell adhesion molecule (EpCAM)-positive PC from GI cancer received 4 sequential intraperitoneal catumaxomab infusions: day 0: 10 mu g; day 3: 10 or 20 mu g; day 7: 30, 50, or 100 mu g; and day 10: 50, 100, or 200 mu g. Dose escalation was guided by dose-limiting toxicities. Results: The MTD was 10, 20, 50, and 200 mu g on days 0, 3, 7, and 10, respectively. Catumaxomab had an acceptable safety profile: Most common treatment-related adverse events (at the MTD) were fever, vomiting, and abdominal pain. At final examination, 11/17 evaluable patients (65%) were progression free: 1 patient had a complete and 3 a partial response. Median overall survival from the time of diagnosis of PC was 502 days. Conclusions: Intraperitoneal catumaxomab is a promising option for the treatment of PC from GI cancer

Component-Resolved Diagnosis (CRD) of Type I Allergy with Recombinant Grass and Tree Pollen Allergens by Skin Testing

The diagnosis of Type I allergy is based on the measurement of allergen-specific IgE antibodies and on provocation with allergens, most frequently conducted by skin testing. Both forms of diagnosis are currently performed with allergen extracts that are difficult to standardize regarding their allergen contents, and which contain additional undefined nonallergenic components. We report the expression in Escherichia coli and purification of some of the most relevant timothy grass- and birch pollen allergens. Recombinant timothy grass- (rPhl p 1, rPhl p 2, rPhl p 5) and birch pollen (rBet v 1, rBet v 2) allergens were purified and used for the measurement of allergen-specific IgE and IgG subclass responses as well as for skin prick testing in 55 pollen allergic patients and 10 nonatopic individuals. Results obtained showed that the recombinant allergens allowed in vivo allergy diagnosis in 52 of 54 of the grass pollen and in 35 of 36 of the birch pollen allergic patients. Positive skin reactions were observed almost exclusively in patients containing detectable allergen-specific IgE antibodies but not in the nonatopic group; however, sensitivity to a given allergen as measured by skin reactivity was weakly correlated with the levels of allergen-specific IgE. Our results demonstrate that recombinant allergens can be used for component-resolved skin test diagnosis (CRD) of the patients’ allergen sensitization profile, whereas allergen extracts at best allow to identify allergen-containing sources. CRD may thus represent the basis for novel forms of patient-tailored immunotherapy

High concentrations of polyelectrolyte complex nanoparticles decrease activity of osteoclasts

Fracture treatment in osteoporotic patients is still challenging. Osteoporosis emerges when there is an imbalance between bone formation and resorption in favor of resorption by osteoclasts. Thus, new implantmaterials for osteoporotic fracture treatment should promote bone formation and reduce bone resorption. Nanoparticles can serve as drug delivery systems for growth factors like Brain-Derived Neurotrophic Factor (BDNF), which stimulated osteoblast differentiation. Therefore, polyelectrolyte complex nanoparticles (PEC-NPs) consisting of poly(l-lysine) (PLL) and cellulose sulfate (CS), with or without addition of BDNF, were used to analyze their effect on osteoclasts in vitro. Live cell images showed that osteoclast numbers decreased after application of high PLL/CS PEC-NPs concentrations independent of whether BDNF was added or not. Real-time RT-PCR revealed that relative mRNA expression of cathepsin K and calcitonin receptor significantly declined after incubation of osteoclasts with high concentrations of PLL/CS PEC-NPs. Furthermore, Enzyme-Linked Immunosorbent Assay indicated that tartrate-resistant acidic phosphatase 5b activity was significantly reduced in the presence of high PLL/CS PEC-NPs concentrations. Consistent with these results, the pit formation analysis showed that less hydroxyapatite was resorbed by osteoclasts after incubation with high concentrations of PLL/CS PEC-NPs. BDNF had no influence on osteoclasts. We conclude that highly concentrated PLL/CS PEC-NPs dosages decreased osteoclastogenesis and osteoclasts activity. Moreover, BDNF might be a promising growth factor for osteoporotic fracture treatment since it did not increase osteoclast activity. © 2019 by the authors