The free-living flatworm Macrostomum lignano: A new model organism for ageing research

To study the several elements and causes of ageing, diverse model organisms and methodologies are required. The most frequently used models are Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster and rodents. All have their advantages and disadvantages and allow studying particular aspects of the ageing process. During the last few years, several ageing studies focussed on stem cells and their role in tissue homeostasis. Here we present a new model organism which can study this relation where other model systems fail. The flatworm Macrostomum lignano possesses a dynamic population of likely totipotent somatic stem cells known as neoblasts. Several characteristics qualify M. lignano as a suitable model system for ageing studies in general and more specifically for gaining more insight in the causal relation between stem cells, ageing and rejuvenation. In this review, we will briefly describe the species and its life history, and discuss the role of its stem cells in ageing and rejuvenation. We also give an overview of the available experimental tools that allow a multidisciplinary approach for studying ageing in M. lignano.     

Early and late components of error monitoring in violent offenders with psychopathy

BACKGROUND: One of the most recognizable features of psychopathy is the reduced ability to successfully learn and adapt overt behavior. This might be due to deficient processing of error information indicating the need to adapt controlled behavior. METHODS: Event-related potentials (ERPs) and behavioral components of error-monitoring processes were investigated in 16 individuals with psychopathy and in 18 healthy subjects. A letter version of the Eriksen flanker task was used in two conditions. The first condition (normal condition) required participants to press one of two buttons depending on the identity of the target stimulus. The second condition (signaling condition) required them to signal each time they had committed an error by making a second press on a signaling button. Early stages of error monitoring were investigated by using the error-related negativity (ERN/Ne) and post-error slowing as indexes. Later stages were explored by examining the error positivity (Pe) and signaling rates. RESULTS: Both groups showed similar ERN amplitudes and amounts of post-error slowing. The psychopathic group exhibited both reduced Pe amplitudes and diminished error-signaling rates compared with the control group. CONCLUSIONS: Individuals with psychopathy show intact early error processing and automatic behavioral adaptation but have deficits in later stages of error processing and controlled behavioral adaptation. This is an indication that individuals with psychopathy are unable to effectively use error information to change their behavior adequately.     

Large conductance calcium-activated potassium channels (BKCa) modulate trigeminovascular nociceptive transmission

Migraine is a common, disabling, neurological problem whose acute management would benefit from the development of purely neurally acting therapies. The trigeminocervical complex is pivotal in nociceptive signaling in migraine, and is an accepted target for putative antimigraine agents. Whole-cell patch-clamp or extracellular recordings were made of trigeminal neurons identified in rat brainstem slices. Bath application of the large conductance calcium-activated potassium (BK_Ca) channel opener NS1619 caused a dramatic decrease of cell firing that could be reversed by the co-application of iberiotoxin. NS1619 hyperpolarized the resting membrane potential and reduced the frequency of spontaneous action potentials in these neurons. These data suggest the presence of BK_Ca channels in the trigeminocervical complex. In vivo in cat l -glutamate-evoked firing was facilitated in nociceptive neurons, also responding to stimulation of the superior sagittal sinus, in the trigeminal nucleus caudalis by the BK_Ca peptide antagonists, iberiotoxin and slotoxin. Of units tested, 70% responded to microiontophoretic application of the blockers, identifying a subpopulation of trigeminal neurons expressing toxin-sensitive BK_Ca channels. NS1619 inhibited 74% of cells tested, and this was reversed by slotoxin, suggesting that the action of NS1619 in these cells was mediated through BK_Ca channels. These data are consistent with the presence of BK_Ca channels in the trigeminal nucleus caudalis that are potential targets for the development of antimigraine treatments, and may also offer insights into receptor mechanisms involved in sensitization and thus allodynia, in migraine.     

Heparin-stimulated inhibition of factor IXa generation and factor IXa neutralization in plasma

Generation and inhibition of activated factor IXa was studied in factor XIa-activated plasma containing 4 mmol/L free calcium ions and 20 mumol/L phospholipid (25 mol% phosphatidylserine/75 mol% phosphatidylcholine). Interference of other (activated) clotting factors with the factor IXa activity measurements could be avoided by using a highly specific and sensitive bioassay. Factor IXa generation curves were analyzed according to a model that assumed Michaelis-Menten kinetics of factor XIa-catalyzed factor IXa formation and pseudo first order kinetics of inhibition of factor XIa and factor IXa. In the absence of heparin, factor IXa activity in plasma reached final levels that were found to increase with increasing amounts of factor XIa used to activate the plasma. When the model was fitted to this set of factor IXa generation curves, the analysis yielded a rate constant of inhibition of factor XIa of 0.7 +/- 0.1 min-1 and a kcat/Km ratio of 0.29 +/- 0.01 (nmol/L)-1 min-1. No neutralization of factor IXa activity was observed (the estimated rate constant of inhibition of factor IXa was 0). Thus, in the absence of heparin, the final level of factor IXa in plasma is only dependent on the initial factor XIa concentration. While neutralization of in situ generated factor IXa in normal plasma was negligible, unfractionated heparin dramatically enhanced the rate of inactivation of factor IXa (apparent second order rate constant of inhibition of 5.2 min-1/per microgram heparin/mL). The synthetic pentasaccharide heparin, the smallest heparin chain capable of binding antithrombin III, stimulated the inhibition of in situ generated factor IXa, but sevenfold less than unfractionated heparin (k = 0.76 min-1 per microgram pentasaccharide/mL). We found that free calcium ions were absolutely required to observe an unfractionated heparin and pentasaccharide-stimulated neutralization of factor IXa activity. Factor XIa inhibition (psuedo first order rate constant of 0.7 min-1) was not affected by unfractionated heparin or pentasaccharide in the range of heparin concentrations studied.     

Trophic feeding of the preterm infant

Trophic feeding is the practice of feeding minute volumes of enteral feeds in order to stimulate the development of the immature gastrointestinal tract of the preterm infant This paper reviews the randomized controlled studies that have examined the physiological and clinical responses to trophic feeding of the preterm infant. Trophic feeding alters gastrointestinal disaccharidase activity, hormone release, blood flow, motility and microbial flora. Clinical benefits appear to include improved milk tolerance, greater postnatal growth, reduced systemic sepsis and shorter hospital stay. There is currently no evidence of any adverse effects following trophic feeding.     

No significant differences in peritoneal fluid handling in children using PH-neutral or acidic solutions.

OBJECTIVES: Differences in peritoneal fluid handling in the acute setting can be expected if children are converted to pH-neutral dialysis solutions because conventional acidic solutions exert toxic effects on peritoneal mesothelial cells and microcirculation. Peritoneal fluid kinetics was therefore investigated with both types of solutions in a group of children. DESIGN: Peritoneal equilibration tests (PETs) were performed in 12 patients [mean age 70 months, mean time on peritoneal dialysis (PD) 18 months] using a pH-neutral PD fluid (Physioneal 3.86%; Baxter Ltd, Castlebar, Ireland) and dextran 70 as a volume marker. The results of these PETs were compared to those of a historic group of 12 children (mean age 75 months, mean time on PD 17 months). SETTING: Pediatric dialysis unit in a tertiary institute. PATIENTS: Stable pediatric PD patients. MAIN OUTCOME MEASURES: Transcapillary ultrafiltration (TCUF) and marker clearance, dialysate-to-plasma (D/P) ratios for urea and creatinine, and D(t)/D(0) ratio for glucose. RESULTS: TCUF and lymphatic absorption were not different between the two groups. There was also no significant difference in small solute clearance measured by D/P ratio for urea and creatinine and D(t)/D(0) ratio for glucose. CONCLUSION: Peritoneal fluid kinetics is not significantly altered if pH-neutral dialysis solutions are applied compared to acidic solutions. An altered TCUF, as is hypothetically possible using an acidic solution, was not established.     

Nucleolar organizer regions in the normal and carcinomatous epithelium of the uterine cervix. A morphometric study

Nonhistone nucleoproteins associated with the nucleolar organizer regions (NORs), the genes coding for the ribosomal RNA precursor, can be visualized by silver staining. The black dots (AgNORs) appearing on the nuclei are thought to reflect cell differentiation. In this study, AgNORs were counted and their area was measured and compared with the area of the nuclei in normal and carcinomatous cells of the uterine cervix. The number of AgNORs per nucleus was significantly higher in the endocervical than in the basal exocervical epithelium (p less than 0.005) and in the carcinomatous epithelium, either in situ or invasive, than in both normal epithelia (p less than 0.002). Individual AgNORs were significantly smaller in carcinoma in situ than in endocervical epithelium (p less than 0.05) or in invasive carcinoma (p less than 0.01). Significant differences were also found in the total AgNORs area per nucleus between the following groups: basal exocervical versus endocervical epithelium (p less than 0.01), basal exocervical and endocervical epithelium versus invasive carcinoma (p less than 0.001), and in-situ versus invasive carcinoma (p = 0.02). The conclusions are that the number and the total area of AgNORs per nucleus increase with the differentiation of the cell or with its carcinomatous transformation, but no prognostic significance can be drawn so far from our measurements.