Inflammatory chemokine expression in the peripheral blood of neonates with perinatal asphyxia and perinatal or nosocomial infections

AIM: The inflammatory response induced by perinatal infections and asphyxia is considered to participate in neonatal brain damage. Inflammatory responses are characterized by the expression of chemokines. Although chemokine levels have been investigated in healthy newborns, their role during neonatal pathological conditions has not been studied. The aim of our study was to examine chemokine serum levels in asphyxiated and infected neonates. METHODS: Peripheral blood samples were obtained from perinatally asphyxiated and infected neonates during the first days of life and from neonates who developed nosocomial infections. Serum levels of interleukin-8 (IL-8), interferon-gamma-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), and regulated upon activation, normal T cells expressed and secreted (RANTES) were determined. RESULTS: In perinatally asphyxiated neonates, IL-8 levels were significantly elevated on the 1st day of life. In perinatally infected neonates, IL-8 and IP-10 levels were significantly increased on the 1st day of life, while RANTES levels were significantly lower and remained so until the 4th day. In nosocomially infected neonates, IL-8, IP-10 and MIP-1alpha levels were significantly increased on diagnosis of infection. CONCLUSION: The neonatal immune system is able to produce chemokines for the induction of an inflammatory response during perinatal asphyxia and perinatal or nosocomial infections. Blockade of inflammatory chemokines could possibly contribute to the prevention of brain damage.     

Effects of the potential 5-HT7 receptor agonist AS 19 in an autoshaping learning task

This work aimed to evaluate further the role of 5-HT7 receptors during memory formation in an autoshaping Pavlovian/instrumental learning task. Post-training administration of the potential 5-HT7 receptor agonist AS 19 or antagonist SB-269970 enhanced memory formation or had no effect, respectively. The AS 19 facilitatory effect was reversed by SB-269970, but not by the selective 5-HT1A antagonist WAY100635. Amnesia induced by scopolamine (cholinergic antagonist) or dizocilpine (NMDA antagonist) was also reversed by AS 19. Certainly, reservations regarding the selectivity of AS 19 for 5-HT7 and other 5-HT receptors in vivo are noteworthy and, therefore, its validity for use in animal models as a pharmacological tool. Having mentioned that, it should be noticed that together these data are providing further support to the notion of the 5-HT7 receptors role in memory formation. Importantly, this 5-HT7 receptor agonist AS 19 appears to represent a step forward respect to the notion that potent and selective 5-HT7 receptor agonists can be useful in the treatment of dysfunctional memory in aged-related decline and Alzheimer's disease.     

Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects

Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD 14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n = 40) compared to control non-diabetic subjects (n = 100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD 14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r = -0.21, p = 0.03, and r = -0.21, p = 0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD 14 and EDVD, r = -0.23, p = 0.023; C-reactive protein and EDVD, r = -0.21, p = 0.03; sCD14 and C-reactive protein, r = 0.30, p = 0.002). In contrast, sCD 14 was positively associated with EDVD in type 2 diabetic patients (r = 0.37, p = 0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r = 0.62, p = 0.001, n = 22). EDVD also correlated with cyclic GMP (r = 0.47, p = 0.03, n = 22). In summary, circulating sCD 14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.     

Can we track the impact of Australian mental health research?

OBJECTIVE: Arguments are being made to increase research and development funding for mental health research in Australia. Consequently, the methods used to measure the results of increased investment require review. This study aimed to describe the status of Australian mental health research and to propose potential methods for tracking changes in research output. Specifically, we describe the research output of nations, Australian states, Australian and New Zealand institutions and Australian and New Zealand researchers using citation rates. METHOD: Information on research output was sourced from two international databases (Institute for scientific information [ISI] Essential Science Indicators and ISI Web of Science) and the ISI list of Highly Cited Researchers. RESULTS: In an international setting, Australia does not perform as well as other comparable countries such as New Zealand or Canada in terms of research output. Within Australia, the scientific performance of institutions apparently relates to the strength of some individual researchers or consolidated research groups. Highly cited papers are evident in the fields of syndrome definition, epidemiology and epidemiological methods, cognitive science and prognostic or longitudinal studies. CONCLUSIONS: Australian researchers need to consider the success of New Zealand and Canadian researchers, particularly given the relatively low investment in health and medical research in New Zealand. Although citation analyses are fraught with difficulties, they can be effectively complemented by other measures of responsiveness to clinical or population needs and community expectations and should be conducted regularly and independently to monitor the status of Australian mental health research.     

Protein dynamics and the immunological evolution of molecular recognition

While it is accepted that protein flexibility plays a role in protein folding, catalysis, and molecular recognition, few techniques are capable of the rigorous measurement of protein motions required to quantify flexibility. Three-pulse photon echo shift spectroscopy can be used to measure the time scale of protein motions, and we have used this technique, along with steady-state spectroscopy and binding and structural data, to examine the immunological evolution of protein flexibility in an anti-fluorescein antibody. Two light chain somatic mutations increase affinity for fluorescein by 12-fold but also significantly affect flexibility. Specifically, a rigidification of the protein is seen in each of three observable motions; two slower motions undergo decreased amplitudes of displacement, by 3- and 20-fold, respectively, in response to an applied force, and the distribution associated with the amplitude of a faster motion is narrowed upon somatic mutation. The somatic mutations appear to rigidify the antibody-fluorescein complex by more strongly anchoring fluorescein to the protein and by more tightly packing the complex. The data demonstrate that in addition to affinity, antibody dynamics are systematically manipulated during affinity maturation, and they imply that the evolution of protein flexibility may be a central component of the immune response. The results also reflect the type of protein rigidification that may be important for other biological interactions, such as protein-protein, protein-ligand or protein-drug, and enzyme-substrate recognition.     

Protective effects of exogenous fructose-1,6-biphosphate during small bowel transplantation in rats

BACKGROUND: We assessed the effect of adding exogenous fructose-1,6-biphosphate (F16BP) to the preservation solution (University of Wisconsin storage solution) used during an experimental procedure of small bowel transplantation in rats. METHODS: We studied levels of the nucleotides hypoxanthine/xanthine and adenosine in tissue after cold ischemia, as well as histologic changes and associated deleterious processes such as bacterial translocation produced by the reperfusion associated with the transplantation. RESULTS: The groups of rats treated with F16BP showed the lowest levels of hypoxanthine/xanthine and uric acid, the highest levels of adenosine, and the lowest levels of histologic damage and lactate dehydrogenase release to the bloodstream. Consumption of intestinal hypoxanthine during reperfusion was lowest in the groups treated with F16BP, as was the incidence of bacterial translocation. CONCLUSIONS: This study shows a protective effect of exogenous F16BP added to University of Wisconsin solution during experimental intestinal transplantation in rats. This protective effect, reflected by decreased intestinal damage and bacterial translocation, was related to a decrease in adenosine triphosphate depletion during cold ischemia before intestinal transplantation, and to the reduced availability of xanthine oxidase substrates for free radical generation during reperfusion.     

Oedema: causes, physiology and nursing management

In this article, Georgina Casey examines the underlying causes of oedema to enable nurses to effectively assess, care and treat patients with this condition.