17β-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes

17β-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5′-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.     

The development of the subplate and thalamocortical connections in the human foetal brain

The aim of this review is to present clinically relevant data on prenatal development of thalamocortical connections in the human brain. The analysis is based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The connection of thalamocortical axons during the ‘waiting’ period with transient cortical subplate zone and subsequent synaptic engagement in the cortical plate is the main connectivity event in the late foetus and preterm infant. This connectivity is the structural substrate for the endogeneous subplate and sensory‐driven circuitry generating transient electrical phenomena and may represent a transient network in the developmental history of consciousness. Conclusion: Findings presented in this review should be considered in the management of pain in preterm infants, in searching for the vulnerability of the subplate zone in diagnostic procedures using the in vivo MRI and in revealing the developmental origin of cognitive and mental disorders.     

Recruitment barriers in a randomized controlled trial from the physicians' perspective – A postal survey

Background  

The feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment.     

Individual differences among cocaine users

The present study examined whether individual differences in personality could differentiate two types of cocaine users. We hypothesized that self-medicators (SM) use cocaine as a way to alleviate their dysphoric moods, whereas sensation seekers (SS), in contrast, use cocaine primarily to engender positive mood states. Eighteen male cocaine users were classified based on two dimensions of the Tridimensional Personality Questionnaire. SM were defined by having high harm avoidance (>17) and low novelty-seeking scores (<18), and SS by high novelty-seeking (>18) and low harm-avoidance scores (<17). It was predicted that SM would report higher depression and anxiety than would SS, and would also exhibit a brain activity pattern similar to that found in clinical depression. The results showed that SM reported higher anxiety than SS, F(1, 8) = 27.5, p < .001, but did not differ in depression. SM exhibited decreased blood flow within the left frontal lobes, F(1, 10) = 6.78, p < .05, similar to what has been observed in major depressive disorder. These findings suggest the importance of attending to individual differences in the motivation for cocaine use so that treatment can be targeted more effectively.     

The Protective Effects of Lactoferrin Feeding against Endotoxin Lethal Shock in Germfree Piglets

The unique germfree, colostrum-deprived, immunologically “virgin” piglet model was used to evaluate the ability of lactoferrin (LF) to protect against lethal shock induced by intravenously administered endotoxin. Piglets were fed LF or bovine serum albumin (BSA) prior to challenge with intravenous Escherichia coli lipopolysaccharide (LPS), and temperature, clinical symptoms, and mortality were tracked for 48 h following LPS administration. Prefeeding with LF resulted in a significant decrease in piglet mortality compared to feeding with BSA (16.7 versus 73.7% mortality, P < 0.001). Protection against the LPS challenge by LF was also correlated with both resistance to induction of hypothermia by endotoxin and an overall increase in wellness, as quantified by a toxicity score developed for these studies. In vitro studies using a flow cytometric assay system demonstrated that LPS binding to porcine monocytes was inhibited by LF in a dose-dependent fashion, suggesting that the mechanism of LF action in vivo may be inhibition of LPS binding to monocytes/macrophages and, in turn, prevention of induction of monocyte/macrophage-derived inflammatory-toxic cytokines.     

Dissociation of the metal inlay from the polyethylene liner in an uncemented threaded cup

We describe a case of spontaneous dissociation of the metal inlay from the polyethylene cup of a sandwiched metal-on-metal total hip prosthesis manufactured from Co-28Cr-6Mo SM 21 alloy. The patient, a 51-year-old active woman, started to feel groin pain 50 months postoperatively. The pain progressed after a slight trauma and led to final revision after 66 months in situ. No signs of impingement were observed. The polyethylene cup showed an approximately 2 mm-deep groove in the superior wall, and the head was heavily worn on the lateral side. In addition to the typically observed abrasive wear patterns, several types of severe wear defects were noticed. Extensive metallosis and necrosis were observed histologically. This unusual case of substantial deformation of the head and the cup was presumed to have occurred as a result of the increased friction and consequent high wear of the metal head.