Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department

Clinical and Experimental Medicine - The aim of the study is to evaluate the prognostic value of early PCSK9 levels in non-intubated septic patients admitted to the emergency department. This...     

I know what I will see: action-specific motor preparation activity in a passive observation task

Literature on mirror neurons has shown that seeing someone preparing to move generates in the motor areas of the observers a brain activity similar to that generated when the subject prepares his own actions. Thus, the ‘mirroring’ of action would not be limited to the execution phase but also involves the preparation process. Here we confirm and extend this notion showing that, just as different brain activities prepare different voluntary actions, also different brain activities prepare to observe different predictable actions. Videos of two different actions from egocentric point of view were presented in separate blocks: (i) grasping of a cup and (ii) impossible grasping of a cup. Subjects had to passively observe the videos showing object-directed hand movements. Through the use of the event-related potentials, we found a cortical activity before observing the actions, which was very similar to the one recorded prior to the actual execution of that same action, in terms of both topography and latency. This anticipatory activity does not represent a general preparation state but an action-specific state, because being dependent on the specific meaning of the forthcoming action. These results reinforce our knowledge about the correspondence between action, perception and cognition.     

Mast cells,glia and neuroinflammation: partners in crime?

Glia and microglia in particular elaborate pro‐inflammatory molecules that play key roles in central nervous system (CNS) disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Microglia respond also to pro‐inflammatory signals released from other non‐neuronal cells, mainly those of immune origin such as mast cells. The latter are found in most tissues, are CNS resident, and traverse the blood–spinal cord and blood–brain barriers when barrier compromise results from CNS pathology. Growing evidence of mast cell–glia communication opens new perspectives for the development of therapies targeting neuroinflammation by differentially modulating activation of non‐neuronal cells that normally control neuronal sensitization – both peripherally and centrally. Mast cells and glia possess endogenous homeostatic mechanisms/molecules that can be up‐regulated as a result of tissue damage or stimulation of inflammatory responses. Such molecules include the N‐acylethanolamine family. One such member, N‐palmitoylethanolamine is proposed to have a key role in maintenance of cellular homeostasis in the face of external stressors provoking, for example, inflammation. N‐Palmitoylethanolamine has proven efficacious in mast‐cell‐mediated experimental models of acute and neurogenic inflammation. This review will provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of microglia, neuroimmune interactions involving mast cells and the possibility that mast cell–microglia cross‐talk contributes to the exacerbation of acute symptoms of chronic neurodegenerative disease and accelerates disease progression, as well as promoting pain transmission pathways. We will conclude by considering the therapeutic potential of treating systemic inflammation or blockade of signalling pathways from the periphery to the brain in such settings.     

Role of law enforcement response and microbial forensics in investigation of bioterrorism

The risk and threat of bioterrorism and biocrime have become a large concern and challenge for governments and society to enhance biosecurity. Law enforcement plays an important role in assessing and investigating activities involved in an event of bioterrorism or biocrime. Key to a successful biosecurity program is increased awareness and early detection of threats facilitated by an integrated network of responsibilities and capabilities from government, academic, private, and public assets. To support an investigation, microbial forensic sciences are employed to analyze and characterize forensic evidence with the goal of attribution or crime scene reconstruction. Two different molecular biology-based assays – real time polymerase chain reaction (PCR) and repetitive element PCR – are described and demonstrate how molecular biology tools may be utilized to aid in the investigative process. Technologies relied on by microbial forensic scientists need to be properly validated so that the methods used are understood and so that interpretation of results is carried out within the limitations of the assays. The three types of validation are preliminary, developmental, and internal. The first is necessary for rapid response when a threat is imminent or an attack has recently occurred. The latter two apply to implementation of routinely used procedures.     

A simplified method for fabrication of new complete dentures

This article discusses a simple technique for fabricating a new set of complete dentures when there is a reasonable existing upper and lower denture pair. This method reduces the number of appointments needed, and may be very helpful in treating patients with transportation difficulties, especially when the dentist is able to perform some simple laboratory procedures such as mounting the case on the articulator. The technique is well-suited for a "worn-out" set of complete dentures.     

Growth hormone response to growth hormone-releasing hormone in normal and uraemic children. Comparison with hypoglycaemia following insulin administration

The uraemic syndrome is characterized by several endocrinological disturbances. This study was undertaken in order to evaluate the GH response to growth hormone-releasing hormone (GRH) in children with chronic renal failure (CRF) and to compare the results with those observed after insulin hypoglycaemia. Twenty-two children with CRF, 10 undergoing continuous ambulatory peritoneal dialysis (CAPD) and 12 on conservative treatment (CT), age ranges 2-15 years, were studied and the data were compared with those from 14 children with normal renal function and normal hormonal behaviour, affected by short stature (NC), and those form 13 healthy adult volunteers (NA). The GRH test (l micrograms/kg body weight, iv) was carried out in 8 CAPD, 8 CT, 9 NC and 10 NA subjects. The blood samples were taken every 30 min for 3 h in CAPD and CT and for 2 h in NC and NA starting at 09.00 h. The following hormones were measured: GH, LH, FSH, Prl, TSH and cortisol (F). The insulin test (0.1 U/kg body weight, iv) was carried out in 5 CAPD, 5 CT, 10 NC and 9 NA on blood samples taken every 30 min for 2 h, measuring GH and glycaemia. No adverse effects were observed after the infusion of GRH. GRH administration induced a prompt response in all subjects, but GH plasma levels were significantly higher in uraemic children than in adults (peak value of 43.5 +/- 8.2, 45.0 +/- 8.4, 27.8 +/- 6.0; 13.5 +/- 2.6 micrograms/ml in CAPD, CT, NC and NA, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Absence of NK1 receptors in human blood lymphocytes and granulocytes

Substance P is a peptide that exerts its activity through the interaction with specific receptors that are distributed in different brain areas. Given the potential of NK1 receptor antagonists as antidepressants, the availability of a peripheral model of NK1 receptors would be particularly relevant for the possibility to perform studies in samples of patients. Therefore, with the present study we aimed to explore the possible existence of NK1 receptors by means of [3H]SR140333 and [125I]BHSP that behave as, respectively, antagonist and agonist, at this level, in human blood lymphocytes and granulocytes of healthy donors. The results of the present study failed to detect the presence of a high-affinity and saturable binding of [3H]SR140333 and [125I]BHSP in human blood cells, whereas a specific binding for both compounds was found in rat cerebral cortex that was used as the control tissue. These findings would question the presence of NK1 receptors in human circulating cells.     

Measurement of glomerular filtration rate in obese patients: pitfalls and potential consequences on drug therapy

Epidemiological studies have shown that obesity is associated with chronic kidney disease and end stage renal disease. These studies have used creatinine derived equations to estimate glomerular filtration rate (GFR) and have indexed GFR to body surface area (BSA). However, the use of equations using creatinine as a surrogate marker of glomerular filtration and the indexation of GFR for BSA can be questioned in the obese population. First, these equations lack precision when they are compared to gold standard GFR measurements such as inulin clearances; secondly, the indexation of GFR for 1.73 m(2) of BSA leads to a systematic underestimation of GFR compared to absolute GFR in obese patients who have BSA that usually exceed 1.73 m(2). Obesity is also associated with pathophysiological changes that can affect the pharmacokinetics of drugs. The effect of obesity on both renal function and drug pharmacokinetics raises the issue of correct drug dosage in obese individuals. This may be particularly relevant for drugs known to have a narrow therapeutic range or excreted by the kidney.