Relationships between cell division,expression of growth factors and microcirculation in the thyroids of Tg-A2aR transgenic mice and patients with Graves' disease

Tissue heterogeneity and nodule formation are hallmarks of thyroid growth. This is accounted for by the clonality theory that acknowledges different individual cellular abilities to respond to trophic stimuli. In order to test the hypothesis that functional and mitotic properties of thyrocytes could be influenced by paracrine interactions with neighbour endothelial cells, studies were conducted in both mouse and human goitre models. In the first part of the study, homogenous goitres in C57 black mice were compared with heterogeneous goitres in transgenic hyperthyroid mice expressing the A2 adenosine receptor (Tg-A2aR). The second part of the study concentrated on comparing human thyroid tIssue of control individuals and of patients with Graves' disease. The rate of cell division was evaluated by immunohistochemical detection of cells positive for proliferating cell nuclear antigen (PCNA). Their spatial distribution was then correlated with immunohistochemical cellular expression of growth- and vasoactive-related factors (fibroblast growth factor-2, transforming growth factor-beta, endothelin-1, vascular endothelial growth factor, nitric oxide synthase III), and with microcirculation expansion. Observations were made on digitalised images of histological serial sections. The nearest-neighbour method was used to distinguish between random or clustered distribution. PCNA-positive cells were both randomly and uniformly distributed in homogenous goitres from C57 black mice, and were clustered in tIssue areas identified as papillary and hyperplastic zones in heterogeneous goitres from Tg-A2aR mice. However, they were absent in the so-called compact cellular zones featuring resting cells. Moreover, whereas papillary and hyperplastic zones were highly vascularised, compact zones were nearly free of microvessels. Spatial distribution of dividing cells was positively correlated with the expression of growth-related factors. A similar pattern was observed in the thyroids of patients with Graves' disease. In accordance with the recent demonstration of the presence of angiofollicular units in the thyroid, these data strongly support the hypothesis that functional and mitotic properties of each single thyrocyte, likely to be responsible for growth heterogeneity of hyperplastic glands, may be adjusted at tIssue level by specific interactions with neighbour endothelial cells that, in turn, could alter the mitotic rate of thyrocytes through paracrine signals.     

The effects of low and moderate intensity exercise on subjective experiences in a naturalistic health and fitness club setting

The purpose of this study was to compare the effects of participation in low and moderate intensity exercise on subjective exercise experiences in a naturalistic health club setting. Thirty physically active members of a community health and fitness club participated in low and moderate intensity cycle ergometry for 20 minutes. Subjective exercise experiences were measured before, during and after exercise. Participants reported significant increases in Positive Well-being and Fatigue scores across time in the moderate but no change in the low exercise intensity condition. The results suggest that exercising for 20 minutes at moderate intensity in a health club environment provides some measure of psychological benefit for a general population, although exercise at the higher intensity could have negative implications by increasing feelings of fatigue during and after exercise.     

Attentional bias in people with acute versus persistent insomnia secondary to cancer

This study investigated the role of attentional bias in the development of persistent insomnia. Two groups of people with cancer who developed sleep-onset problems 0-3 months and 12-18 months after diagnosis completed a computerized emotional Stroop task comprising cancer-related and sleep-related word cues and self-complete measures. Both groups demonstrated attentional bias for cancer-related words, but only the persistent insomnia group demonstrated attentional bias for sleep-related words. High levels of presleep cognitive arousal were evident in both groups despite lower levels of psychological distress in the persistent insomnia group. Results suggest that secondary, sleep-related mental preoccupation may inhibit recovery to normal sleep after stress-related acute sleep disturbance. Findings are discussed in relation to current models of insomnia.     

A perspective on the measurement of ADAMTS13 in thrombotic thrombocytopaenic purpura

The recent discovery of the von Willebrand Factor (vWF) cleaving protease (ADAMTS13) and the association of its deficiency with thrombotic thrombocytopaenic purpura (TTP) has generated both enormous interest and considerable confusion. Ultra large von Willebrand Factor (UL vWF) multimers are present in the plasmas of patients with chronic relapsing TTP in remission but disappear during an attack. This observation led to the recognition that UL vWF multimers precipitate the thrombotic occlusion of arterioles, a feature that characterizes TTP. Multiple mutations in ADAMTS13 are associated with congenital TTP and neutralizing autoantibodies have been demonstrated in the acquired TTP syndrome. Although a number of functional assays for this enzyme have been described, the more rigorously evaluated assays are difficult to perform outside a research laboratory. There is also an enduring uncertainty about the specificity of ADAMTS13 deficiency for the diagnosis of acquired TTP and a perception that the result does not alter patient management. The cloning of the ADAMTS13 gene has also raised the prospect of recombinant enzyme therapy for the treatment of TTP, and this has heightened the need for a simple assay. In this review, we evaluate the value of measuring this enzyme in the management of TTP.     

Cytotoxicity of glutaraldehyde crosslinked collagen/poly(vinyl alcohol) films is by the mechanism of apoptosis

Collagen has been investigated as a potential natural biomaterial, because of its occurrence in the extracellular matrix. Collagen requires crosslinking in this context, by reagents that are often cytotoxic. Glutaraldehyde is one such agent that is potentially cytotoxic. The aim of this study was to determine the cause of poor cell attachment and growth on collagen/poly(vinyl alcohol) bioartificial composite films, when crosslinked with glutaraldehyde. Dehydrothermal crosslinking was used as a comparison. Human osteoblasts were observed to undergo apoptosis on glutaraldehyde crosslinked films dependent on concentration of collagen present. Higher collagen content resulted in higher levels of apoptosis with poor cell attachment and spreading of remaining cells. Post-treatment of films with 8% L-glutamic acid prevented the apoptotic response of osteoblasts and allowed attachment and spreading. The addition of 100 nM insulin-like growth factor-1 to the culture medium also prevented apoptosis. Glutaraldehyde toxicity of crosslinked collagen has been demonstrated in this study, the mechanism of which is apoptosis. This study indicates that poor biocompatibility and induction of apoptosis on collagen/poly(vinyl alcohol) films crosslinked by glutaraldehyde are attributed to glutaraldehyde components on the surface of the films (not residual glutaraldehyde), whose effects can be quenched by glutamic acid, and prevented by insulin-like growth factor-1.     

Poly(epsilon-caprolactone) and poly(epsilon-caprolactone)-polyvinylpyrrolidone-iodine blends as ureteral biomaterials: characterisation of mechanical and surface properties,degradation and resistance to encrustation in vitro

This study describes the physicochemical properties and in vitro resistance to encrustation of solvent cast films composed of either poly(epsilon-caprolactone) (PCL), prepared using different ratios of high (50,000) to low (4000) (molecular weight) m.wt., or blends of PCL and the polymeric antimicrobial complex, poly(vinylpyrrolidone)-iodine (PVP-I). The incorporation of PVP-I offered antimicrobial activity to the biomaterials. Films were characterised in terms of mechanical (tensile analysis, dynamic mechanical thermal analysis) and surface properties (dynamic contact angle analysis, scanning electron microscopy), whereas degradation (at 37 degrees C in PBS at pH 7.4) was determined gravimetrically. The resistance of the films to encrustation was evaluated using an in vitro encrustation model. Reductions in the ratio of high:low-m.wt. PCL significantly reduced the ultimate tensile strength, % elongation at break and the advancing contact angle of the films. These effects were attributed to alterations in the amorphous content and the more hydrophilic nature of the films. Conversely, there were no alterations in Young's modulus, the viscoelastic properties and glass-transition temperature. Incorporation of PVP-I did not affect the mechanical or rheological properties of the films, indicative of a limited interaction between the two polymers in the solid state. Manipulation of the high:low m.wt. ratio of PCL significantly altered the degradation of the films, most notably following longer immersion periods, and resistance to encrustation. Accordingly, maximum degradation and resistance to encrustation was observed with the biomaterial composed of 40:60 high:low m.wt. ratios of PCL; however, the mechanical properties of this system were considered inappropriate for clinical application. Films composed of either 50:50 or 60:40 ratio of high:low m.wt. PCL offered an appropriate compromise between physicochemical properties and resistance to encrustation. This study has highlighted the important usefulness of degradable polymer systems as ureteral biomaterials.     

Parent visual analogue scale ratings of children's pain do not reliably reflect pain reported by child

OBJECTIVES: To determine whether parent and child visual analogue scale (VAS) scores for the pain associated with acute conditions in the child agree sufficiently for these methods of measurement to be considered interchangeable in pain and analgesia research. DESIGN: This was a prospective, two-group, repeated measures, blinded study in an urban pediatric emergency department. Children aged 8 to 15 years seeking treatment for painful conditions and the parents of these children were asked to rate the child's pain independently using a VAS on as many as four occasions at 20-minute intervals. Both participants were blinded to their previous rating and the rating of the other participant. The main outcome measure was the correlation of child and parent VAS pain scores by Pearson correlation and bias plot (Bland-Altman) analysis of agreement between tests. RESULTS: Seventy-eight child-parent sets participated, yielding 289 VAS pain score comparison pairs for evaluation. The correlation between child and parent VAS pain scores was 0.63 (95% CI, 0.56-0.70). Bias plot analysis revealed a bias of 5% and 95% limits of agreement from -38 to +47 mm. The degree of difference between child and parent scores was variable, but there was an increasing tendency for parents to underestimate the child's pain when the child recorded VAS pain scores at the higher end of the scale. CONCLUSIONS: Parents' VAS score ratings of their children's pain correlate only moderately with the children's VAS pain scores and show poor levels of agreement. The difference between the measures is variable and appears to be more marked when the child reports a higher VAS score. This research raises doubt about whether parental rating of a child's pain is an appropriate surrogate marker in pediatric pain and analgesia research.     

Predictors of 30-month outcome after perinatal depression: role of proton MRS and socioeconomic factors

The objective was to determine in infants with perinatal depression whether the relative concentrations of N-acetylaspartate and lactate in the neonatal period are associated with (1) neurodevelopmental outcome at 30 mo of age or (2) deterioration in outcome from age 12 to 30 mo; and to determine whether socioeconomic factors are associated with deterioration in outcome. Thirty-seven term neonates were prospectively studied with single-voxel proton magnetic resonance spectroscopy of the basal nuclei and intervascular boundary zones. Thirty-month outcomes were classified as normal [if Mental Development Index of the Bayley Scales of Infant Development (MDI) >85 and neuromotor scores (NMS) <3; n = 15], abnormal [if MDI or=3 at 12 and 30 mo; n = 11], or deteriorated [if normal at 12 mo and abnormal at 30 mo (MDI or=3); n = 11]. Thirty percent (11/37) of our cohort deteriorated between 12 and 30 mo. N-acetylaspartate/choline decreased across the groups ordered as normal, deteriorated, and abnormal [in basal nuclei (p 相似文献