Endoscopic tattoo of the colon might be standardized to locate tumors intraoperatively

BACKGROUND: Small colonic lesions which are identified during endoscopy are usually difficult to locate intra-operatively. Endoscopic tattoo of the colon seems the most efficient method, however it does fail in some cases to identify the lesion peroperatively. We studied this method to evaluate its efficacy. METHODS: Nineteen patients were tattooed during colonoscopy with "India ink" (drawing ink Rotring ). These patients had lesions in which difficulties were anticipated when retracing them again during colorectal surgery. Seventeen patients underwent colonic surgery. One patient underwent laparoscopic polypectomy and the other TEM (Transanal Endoscopic Microsurgery). RESULTS: The visibility of the "India ink" peroperatively and afterwards during histological examination were evaluated. The tattoos were visible in 68.4 % patients intraoperatively. Histopathological macroscopic examination of the specimens showed ink in 73.6 % patients. In 31.5 % patients the tattoo could not be recognised peroperatively. CONCLUSIONS: Endoscopy assisted tattooing of the colon has been reported to be a safe method to landmark lesions in the colon. In the majority of our patients the tattoo was obvious during surgery. Endoscopic tattoo seems an efficient technique in identifying small colonic lesions intraoperatively.     

Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction

OBJECTIVES: We assessed the effects of erythropoietin (EPO) treatment in a rat model of post-myocardial infarction (MI) heart failure. BACKGROUND: Erythropoietin, traditionally known as a hematopoietic hormone, has been linked to neovascularization. Whereas administration of EPO acutely after MI reduces infarct size and improves cardiac function, its role in the failing heart is unknown. METHODS: Rats underwent coronary ligation or sham surgery. Rats with MI were randomly assigned to: untreated (MI), a single bolus of EPO immediately after MI induction (MI-EPO-early), EPO treatment immediately after MI and once every three weeks (MI-EPO-early+late), and EPO treatment starting three weeks after induction of MI, once every three weeks (MI-EPO-late). After nine weeks, hemodynamics, infarct size, myosin heavy chain (MHC) isoforms, myocyte hypertrophy, and capillary density were measured. RESULTS: Erythropoietin treatment started immediately after MI (MI-EPO-early and MI-EPO-early+late) resulted in a 23% to 30% reduction in infarct size (p < 0.01) and, accordingly, hemodynamic improvement. Erythropoietin treatment, started three weeks after MI (MI-EPO-late), did not affect infarct size, but resulted in an improved cardiac performance, reflected by a 34% reduction in left ventricular end-diastolic pressure (p < 0.01), and 46% decrease in atrial natriuretic peptide levels (p < 0.05). The improved cardiac function was accompanied by an increased capillary density (p < 0.01), an increased capillary-to-myocyte ratio (p < 0.05), and a partial reversal of beta-MHC (p < 0.05) in all treated groups. CONCLUSIONS: In addition to its effect on infarct size reduction, EPO treatment improves cardiac function in a rat model of post-MI heart failure. This observation may be explained by neovascularization, associated with an increased alpha-MHC expression.     

Plasma-treated polystyrene surfaces: model surfaces for studying cell-biomaterial interactions

Biocompatibility of biomaterials relates, amongst others, to the absence of adverse cellular reactions and modulation of cell adhesion and subsequent responses. With respect to tissue-engineering applications, most materials need to evoke cell adhesion and spreading, while potentially displaying differential cell function. Adhesion has frequently been studied in a controlled fashion, using adhesion-supporting and -inhibiting substrata. The aim of this study is to create a panel of related materials with gradually changing surface characteristics in order to sustain similar individual cell adhesion and spreading, yet different cell population behaviour. A series of polystyrene materials was created with increasing oxygen surface incorporation and, concurrently, decreasing water-contact angles. Individual cells adhered and spread on all surfaces whilst showing well-developed focal adhesions and stress fibres. Cell populations demonstrated a decreased growth on surfaces with lower wettability. The biochemical activity of cell populations was not influenced by the surface treatment, but cell proliferation on surfaces increased with increasing oxygen incorporation. Furthermore, surface coverage with assembled fibronectin matrix was higher on the substrata with higher wettability. Finally, the expression of the adhesion-related proteins cadherin-5, focal adhesion kinase and RhoA was increased on surfaces with higher wettability. Further explorations of the cell biological basis of the observed differential behaviour will give more detailed answers on the rules governing cell-material interactions.     

Taking the community into the home

The changing demographics of the population are such that there is an increasing need for care for frail older people with both physical and mental health problems. At the same time, the increased migration of workers and their families means that care provision now has to embrace a range of cultures. The present paper explores how the concept of cultural safety has importance for those planning and providing care for older adults. The recognition that removing individuals with mental health problems from their own environment causes increased disorientation and confusion has led to some organisations trying to maintain the community aspects of life when independent living is no longer possible. The present paper focuses on two such organisations in the Netherlands, demonstrating how they have changed their practice to improve and enhance the quality of life of their clientele through 'taking the community into the home'. Whilst sharing the same goals and aspirations, each organisation, serves a different population, and therefore, has developed a unique approach.     

Growth factor-induced contraction of human bronchial smooth muscle is Rho-kinase-dependent

Growth factors have been implicated in the pathophysiology of asthma. However, the putative effects of these growth factors on human airway smooth muscle tone are still largely unknown. We performed contraction experiments using human bronchial smooth muscle ring preparations. The growth factor insulin-like growth factor-1 (IGF-1) induced a slowly developing sustained contraction, which was dependent on Rho-kinase, since contraction was almost completely inhibited by (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide (Y-27632; 1 microM). Angiotensin II, a G(q)-coupled receptor agonist which can act as a growth factor as well, induced a biphasic contraction, the sustained phase of which was also almost completely inhibited by Y-27632. We conclude that angiotensin II and IGF-1 induce a Rho-kinase-dependent sustained contraction of human bronchial smooth muscle. Since growth factors are associated with pathophysiological conditions such as asthma, inhibition of Rho-kinase could be effective under these conditions.     

Synthesis and biological evaluation of 2,3,5-substituted [1,2,4]thiadiazoles as allosteric modulators of adenosine receptors

A number of 2,3,5-substituted [1,2,4]thiadiazole analogues of SCH-202676 (N-(2,3-diphenyl[1,2,4]thiadiazole-5(2H)-ylidene)methanamine, 7a) were synthesized and tested as potential allosteric modulators of adenosine receptors. All compounds were capable of displacing the binding of the radiolabeled agonist [(3)H]CCPA to human A(1) adenosine receptors, whereas modest and varying effects were observed on the binding of [(3)H]DPCPX, a radiolabeled antagonist for this receptor subtype. Four compounds, 7a (SCH-202676), 7k (LUF5792), 7l (LUF5794), and 8e (LUF5789), were selected for more detailed characterization. They all proved allosteric inhibitors of agonist binding, with 7k being most potent, whereas their effects on antagonist binding were more ambiguous. Subsequently, experiments were done on human adenosine A(2A) and A(3) receptors. Compounds 7a and 7l displayed peculiar displacement characteristics of both radiolabeled agonist and antagonist binding to A(2A) receptors, whereas 7a showed some activity on A(3) receptors.     

2,4,6-trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists

Adenosine receptor antagonists usually possess a bi- or tricyclic heteroaromatic structure at their core with varying substitution patterns to achieve selectivity and/or greater affinity. Taking into account molecular modeling results from a series of potent adenosine A1 receptor antagonists, a pharmacophore was derived from which we show that a monocyclic core can be equally effective. To achieve a compound that may act at the CNS we propose imposing a restriction related to its polar surface area (PSA). In consequence, we have synthesized two novel series of pyrimidines, possessing good potency at the adenosine A1 receptor and desirable PSA values. In particular, compound 30 (LUF 5735) displays excellent A1 affinity (Ki = 4 nM) and selectivity (< or =50% displacement of 1 muM concentrations of the radioligand at the other three adenosine receptors) and has a PSA value of 53 A2.     

Stress-induced hyperthermia in the mouse: c-fos expression, corticosterone and temperature changes

In mammals, stress exposure is frequently associated with an elevated body temperature ['emotional fever', stress-induced hyperthermia (SIH)]. Rectal measurement of body core temperature of the mouse induces a rise of 1-1.5 degrees C over a 10- to 15-min time interval. This phenomenon has been exploited to design a specific test for measuring stress-induced hyperthermia: the singly-housed SIH paradigm in mice. In the present experiments, changes in body temperature and corticosterone levels were studied 10, 30, 60, 90 and 120 min after the first insertion of the rectal probe. In addition, changes in patterns of neural activation, as observed after immunostaining for Fos-immunoreactivity (Fos-IR), were studied in the brains of animals perfused at times 0, 60 or 120 min. Our results show that SIH and corticosterone levels have their peak values between 10 and 30 min and are no longer different from control values after 60 min. Patterns of Fos-IR have been studied in 11 brain areas, of which 2 brain areas (anterodorsal preoptic and periolivary nuclei) showed a continuing rise in Fos-IR after 60 and 120 min, while six nuclei, mostly hypothalamic and septal, showed a peak induction of Fos-IR after 60 min. In three brain areas, no consistent changes in Fos-IR could be observed. The authors conclude that the changes observed in the patterns of Fos-IR, after application of the singly-housed SIH-test in mice, reflect the effects of both the stressor application and the ensuing thermoregulatory responses. The role of each activated brain area in either one of these effects is discussed in view of data available from the literature.