Prenatal Sonographic Diagnosis of Premature Constriction of the Fetal Ductus Arteriosus After Maternal Self‐Medication With Benzydamine Hydrochloride

We report 3 cases of prenatal diagnosis of premature constriction of the ductus arteriosus after maternal benzydamine hydrochloride therapy (3‐mg lozenges) in third‐trimester pregnancies. In each case, fetal echocardiography revealed a dilated, hypocontractile right ventricle with severe tricuspid regurgitation and constriction of the ductus arteriosus. Although the effect of indomethacin and other nonsteroidal anti‐inflammatory drugs on prenatal ductal constriction is well known, readily available over‐the‐counter nonsteroidal anti‐inflammatory drugs such as benzydamine can have an equally deleterious effect and are best avoided in the third trimester of pregnancy.     

The elemental changes occurring in the rat liver after exposure to PEG-coated iron oxide nanoparticles: total reflection x-ray fluorescence (TXRF) spectroscopy study

The main goal of this study was to evaluate in vivo effects of low dose of PEG-coated magnetic iron oxide nanoparticles (IONPs) on the rat liver. The IONPs was intravenously injected into rats at a dose equaled to 0.03?mg of Fe per 1?kg of an animal body weight. The elemental composition of liver tissue in rats subjected to IONPs action and controls were compared. Moreover, in order to determine the dynamics of nanoparticles (NPs) induced elemental changes, the tissues taken from animals 2?hours, 24?hours, and 7?days from IONPs injection were examined. The analysis of subtle elemental anomalies occurring as a result of IONPs action required application of highly sensitive analytical method. The total reflection X-ray fluorescence spectroscopy perfectly meets such requirements and therefore it was used in this study. The obtained results showed increasing trend of Fe level within liver occurring 2?hours from IONPs injection. One day after NPs administration, the liver Fe content presented the baseline level what suggests only the short-term accumulation of nanoparticles in the organ. The Ca, Cu, and Zn levels changed significantly as a result of NPs action. Moreover, the anomalies in their accumulation were still observed 7?days after IONPs injection. The level of Cu decreased while those of Ca and Zn increased in the liver of NPs-treated animals. The reduced liver Cu, followed by elevated serum level of this element, might be related in triggering the mechanisms responsible for Fe metabolism in the organism.     

Enhanced creativity in bipolar disorder patients: a controlled study

OBJECTIVE: Associations between eminent creativity and bipolar disorders have been reported, but there are few data relating non-eminent creativity to bipolar disorders in clinical samples. We assessed non-eminent creativity in euthymic bipolar (BP) and unipolar major depressive disorder (MDD) patients, creative discipline controls (CC), and healthy controls (HC). METHODS: 49 BP, 25 MDD, 32 CC, and 47 HC (all euthymic) completed four creativity measures yielding six parameters: the Barron-Welsh Art Scale (BWAS-Total, and two subscales, BWAS-Dislike and BWAS-Like), the Adjective Check List Creative Personality Scale (ACL-CPS), and the Torrance Tests of Creative Thinking--Figural (TTCT-F) and Verbal (TTCT-V) versions. Mean scores on these instruments were compared across groups. RESULTS: BP and CC (but not MDD) compared to HC scored significantly higher on BWAS-Total (45% and 48% higher, respectively) and BWAS-Dislike (90% and 88% higher, respectively), but not on BWAS-Like. CC compared to MDD scored significantly higher (12% higher) on TTCT-F. For all other comparisons, creativity scores did not differ significantly between groups. CONCLUSIONS: We found BP and CC (but not MDD) had similarly enhanced creativity on the BWAS-Total (driven by an increase on the BWAS-Dislike) compared to HC. Further studies are needed to determine the mechanisms of enhanced creativity and how it relates to clinical (e.g. temperament, mood, and medication status) and preclinical (e.g. visual and affective processing substrates) parameters.     

The influence of non‐HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

Non‐HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti‐angiotensin II type 1‐receptor‐activating antibodies (anti‐AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti‐AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti‐AT1R antibodies in 117 consecutive renal transplant recipients in pre‐ and post‐transplant screening. Anti‐AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti‐AT1R(+) group. The patients with anti‐AT1R Abs >9 U/ml lost their graft more often. Biopsy‐proven AR was described in 4/27 (15%) pts in the anti‐AT1R(+) group and 13/90 (14.4%) in the anti‐AT1R(?) group, but more severe cases of Banff IIB or antibody‐mediated rejection (AMR) were more often observed in anti‐AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti‐AT1R(+) (P = 0.009). Patients with anti‐AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti‐AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti‐AT1R‐positive ones lost the graft. Our study suggests monitoring of anti‐AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.     

Increased postoperative myeloperoxidase concentration associated with low baseline antioxidant capacity as the risk factor of delirium after cardiac surgery

BackgroundThough risk factors of postoperative delirium are well described, its pathophysiology is still undiscovered. The primary objective of the current study is to assess whether increased pre- and postoperative myeloperoxidase (MPO) levels are associated with postoperative delirium in the population of cardiac surgery patients. The secondary objective is to evaluate the correlation between MPO levels and serum antioxidant capacity (AC).MethodsThe patients’ cognitive status was assessed one day preoperatively with the use of the Mini-Mental State Examination Test and the Clock Drawing Test. A diagnosis of major depressive disorder and anxiety disorders was established based on DSM-5 criteria. Blood samples for MPO and AC levels were collected both pre- and postoperatively. The Confusion Assessment Method for the Intensive Care Unit was used to screen for a diagnosis of delirium.ResultsDelirium occurred in 34% (61 of 177) of patients. Multivariable logistic regression analysis revealed that increased postoperative MPO concentration was independently associated with postoperative delirium development, and negatively correlated with lower baseline serum AC.ConclusionsCardiac surgery patients with less efficient antioxidative mechanisms experience a higher postoperative peak of serum MPO, which in turn may predispose to postoperative delirium development.

KEY MESSAGES

• MPO is a lysosomal enzyme with strong pro-oxidative and pro-inflammatory properties.
• Cardiac surgery patients who have increased concentration of postoperative MPO are at significantly higher risk of postoperative delirium development.
• This higher level of postoperative MPO is negatively correlated with baseline antioxidant capacity (AC).
• It can be hypothesized that individuals with decreased baseline AC experience a higher peak of MPO post-surgery due to less efficient antioxidative mechanisms, which in turn contributes to postoperative delirium development.

     

Aven‐mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma

Conventional high‐grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis‐free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti‐apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G₂ cell‐cycle arrest; Chk1 protein levels were attenuated and ATR–Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven‐depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven‐controlled ATR–Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix‐embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR–Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Behavioural effects of fluoxetine and tianeptine, two antidepressants with opposite action mechanisms, in rats

The behavioural effects of two antidepressants with opposite molecular mechanisms, tianeptine 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin - 11-yl)amino]heptanoic acid S,S-dioxide, CAS 66981-73-5) 5 mg/kg p.o., a serotonin reuptake enhancer, and fluoxetine (+/-)-N-methyl-3-phenyl-3-[(alpha, alpha, alpha-trifluoro-p- tolyl)oxy]propylamine, CAS 54910-89-3) 5 mg/kg p.o., a serotonin reuptake inhibitor, were compared after single and prolonged administration (7 and 14 days) once daily). In all experiments the drug effects were noted at the peak activity time: 30 min after tianeptine and 60 min after fluoxetine administration. In the immobility time test both drugs had a shortening effect on immobility time only after prolonged administration or, in single treatment, after joint administration. A different pattern was observed in the two compartment test: both antidepressants showed anxiolytic effects after single and prolonged treatment. However, when the drugs were given in joint administration, the anxiolytic effects were entirely abolished after single as well as prolonged treatment. In reference spatial memory test (food finding time in the maze) tianeptine had no effect, whereas fluoxetine caused, after single and prolonged treatment, a very marked improvement of reference memory. Joint administration of both drugs resulted in worsening the effects on memory in comparison to fluoxetine alone, but the results were still significantly better vs. control. In the test for sedative action (in the Activity Meter AM-1, where the movements of the animals are counted electronically) only after prolonged treatment with tianeptine a diminished locomotor activity could be observed. It is concluded that in the action of the drugs (beside the effect on serotonin uptake) other mechanisms must play an important role. The diminished locomotor activity after tianeptine suggests an influence on the dopaminergic or GABA-Receptor system.     

Long-term changes in postnatal susceptibility to pilocarpine-induced seizures in rats exposed to gamma radiation at different stages of prenatal development

PURPOSE: To determine whether brains irradiated at different stages of prenatal development also have different postnatal susceptibility to seizures evoked by pilocarpine. METHODS: Pregnant Wistar rats were exposed to a single 1.0-Gy dose of gamma rays on gestation days 13, 15, 17, or 19 (E13, E15, E17, and E19, respectively). On postnatal day 60, their offspring received i.p. pilocarpine injections to evoke status epilepticus. Behavior of the animals was observed continuously for 6 h after the injection, and motor manifestations of seizure activity were rated, and survival times recorded. After 7-day survival, the animals were killed, and their brains were weighed. RESULTS: The average brain weight of animals exposed to irradiation at earlier prenatal stages (E13 or E15) was significantly lower than that after irradiation on E17 or E19. However, effects of the irradiation on the susceptibility to pilocarpine-induced seizures were quite opposite. The intensity of status epilepticus evoked in rats irradiated on E13 or E15 was significantly lower than that in nonirradiated controls or in those irradiated on E17 or E19. Moreover, after irradiation on E13 or E15, survival of the animals was significantly higher in relation not only to other irradiated groups but also to the controls. CONCLUSIONS: The results suggest than the extent of neuronal deficit, even if relatively greater, cannot always lead to higher susceptibility of the dysplastic brain to seizures. Functional consequences of the deficit, even if its magnitude is relatively smaller but involving specific brain areas, appear to be critical for the epileptogenesis.