The dichotomy in the DNA-binding behaviour of ruthenium(II) complexes bearing benzoxazole and benzothiazole groups

The substituted tris(bipyridine)ruthenium(II) complexes {[Ru(bpy)(2)(4,4'-bbob)](2+) and [Ru(bpy)(2)(5,5'-bbob)](2+) [where bpy = 2,2'-bipyridine and bbob = bis(benzoxazol-2-yl)-2,2'-bipyridine] have been prepared and compared to the previously studied complex [Ru(bpy)(2)(4,4'-bbtb)](2+) [where bbtb = bis(benzothiazol-2-yl)-2,2'-bipyridine]. From the UV/VIS titration studies, Delta-[Ru(bpy)(2)(4,4'bbob)](2+) displays a stronger association than the Lambda-isomer with calf-thymus DNA (ct-DNA). For [Ru(bpy)(2)(5,5'-bbob)](2+), there appears to be minimal interaction with ct-DNA. The results of fluorescence titration studies suggest that [Ru(bpy)(2)(4,4'-bbob)](2+) gives an increase in emission intensity with increasing ct-DNA concentrations, with an enantiopreference for the A isomer, confirmed by membrane dialysis studies. The fluorescent intercalation displacement studies revealed that [Ru(bpy)(2)(4,4'-bbob)](2+) and [Ru.(bpy)(2)(5,5'bbob)](2+) display a preference for more open DNA structures such as bulge and hairpin sequences. While Delta-[Ru(bpy)(2)(4,4'-bbtb)](2+) has shown the most significant affinity for all the oligonucleotides sequences screened in previous studies, it is the A isomer of the comparable benzoxazole ruthenium(II) complex (Delta-[Ru(bpy)(2)(4,4'-bbob)](2+)) that preferentially binds to DNA.

The costs of bearing arms and armour in the hermit crab Pagurus bernhardus

Hermit crabs use empty gastropod shells as protective armour and enlarged chelipeds as signals and weapons. However, carrying armour and arms may impose energy costs that result in increased lactate and hence potential fatigue and there may be consequent effects on general activity. We investigated whether variation in shell and cheliped size influences lactate levels in hermit crabs. Lactate was positively related to residual cheliped size for both sexes and was higher in males than females; when we controlled for body size, the former had larger chelipeds. Shell weight unexpectedly had no effect on lactate but crabs in small shells had high lactate, possibly because of reduced ability to maintain a respiratory current. The size of natural shells had no effect on activity but the addition of food odour increased locomotion. However, activity was not related to lactate. We conclude that possession of larger chelipeds than expected for body size imposes significant costs and may limit development of sexual dimorphism. (C) 2010 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Computer simulating a trial of a load-bearing implant: example of an intramedullary prosthesis

Computational modelling is becoming ever more important for obtaining regulatory approval for new medical devices. An accepted approach is to infer performance in a population from an analysis conducted for an idealised or ‘average’ patient; we present here a method for predicting the performance of an orthopaedic implant when released into a population—effectively simulating a clinical trial. Specifically we hypothesise that an analysis based on a method for predicting the performance in a population will lead to different conclusions than an analysis based on an idealised or ‘average’ patient. To test this hypothesis we use a finite element model of an intramedullary implant in a bone whose size and remodelling activity is different for each individual in the population. We compare the performance of a low Young’s modulus implant (View the MathML source) to one with a higher Young’s modulus (200 GPa). Cyclic loading is applied and failure is assumed when the migration of the implant relative to the bone exceeds a threshold magnitude. The analysis for an idealised of ‘average’ patient predicts that the lower modulus device survives longer whereas the analysis simulating a clinical trial predicts no statistically-significant tendency (p=0.77) for the low modulus device to perform better. It is concluded that population-based simulations of implant performance–simulating a clinical trial–present a very valuable opportunity for more realistic computational pre-clinical testing of medical devices.

The effect of hypobaric hypoxia on misonidazole binding in normal and tumour-bearing mice

The effect of hypobaric hypoxia on the in vivo binding of misonidazole was investigated in normal mice and mice bearing T50/80 or CA NT mammary carcinomas. After the intraperitoneal injection of radiolabelled misonidazole, mice were randomised to breathe either room air or air at 0.5 atmospheres. The distribution of misonidazole in liver, kidney, heart, spleen and tumour tissue, 24 h later, was studied by scintillation counting and by autoradiography. Significantly higher misonidazole binding occurred in the livers (x2.5), kidneys (x2.4), spleens (x2.9) and hearts (x1.8) of hypoxic mice compared to controls. Hypobaric hypoxia was associated with a greater than four-fold increase in misonidazole binding within T50/80 tumours. However, significantly higher binding was not demonstrated within CA NT tumours after exposure of tumour-bearing animals to hypoxic conditions. In autoradiographs of hypoxic liver, labelling was intense in regions near to hepatic veins but sparse in areas surrounding portal tracts. This pattern was striking and consistent. In hypoxic kidney, labelling was most intense over tubular cells, less intense over glomeruli and sparse in the renal medulla. It is likely that the hepatic and renal cortical distributions of misonidazole binding reflect local oxygen gradients.

The impedance cardiogram recorded through two electrocardiogram/defibrillator pads as a determinant of cardiac arrest during experimental studies

OBJECTIVE: Laypersons are poor at emergency pulse checks (sensitivity 84%, specificity 36%). Guidelines indicate that pulse checks should not be performed. The impedance cardiogram (dZ/dt) is used to assess stroke volume. Can a novel defibrillator-based impedance cardiogram system be used to distinguish between circulatory arrest and other collapse states?

DESIGN: Animal study.

SETTING: University research laboratory.

SUBJECTS: Twenty anesthetized, mechanically ventilated pigs, weight 50-55 kg.

INTERVENTIONS: Stroke volume was altered by right ventricular pacing (160, 210, 260, and 305 beats/min). Cardiac arrest states were then induced: ventricular fibrillation (by rapid ventricular pacing) and, after successful defibrillation, pulseless electrical activity and asystole (by high-dose intravenous pentobarbitone).

MEASUREMENTS AND MAIN RESULTS: The impedance cardiogram was recorded through electrocardiogram/defibrillator pads in standard cardiac arrest positions. Simultaneously recorded electro- and impedance cardiogram (dZ/dt) along with arterial blood pressure tracings were digitized during each pacing and cardiac arrest protocol. Five-second epochs were analyzed for sinus rhythm (20 before ventricular fibrillation, 20 after successful defibrillation), ventricular fibrillation (40), pulseless electrical activity (20), and asystole (20), in two sets of ten pigs (ten training, ten validation). Standard impedance cardiogram variables were noncontributory in cardiac arrest, so the fast Fourier transform of dZ/dt was assessed. During ventricular pacing, the peak amplitude of fast Fourier transform of dZ/dt (between 1.5 and 4.5 Hz) correlated with stroke volume (r2 = .3, p < .001). In cardiac arrest, a peak amplitude of fast Fourier transform of dZ/dt of < or = 4 dB x ohm x rms indicated no output with high sensitivity (94% training set, 86% validation set) and specificity (98% training set, 90% validation set).

CONCLUSIONS: As a powerful clinical marker of circulatory collapse, the fast Fourier transformation of dZ/dt (impedance cardiogram) has the potential to improve emergency care by laypersons using automated defibrillators.

Detection of cardiac arrest using a simplified frequency analysis of the impedance cardiogram recorded from defibrillator pads

An algorithm based only on the impedance cardiogram (ICG) recorded through two defibrillation pads, using the strongest frequency component and amplitude, incorporated into a defibrillator could determine circulatory arrest and reduce delays in starting cardiopulmonary resuscitation (CPR). Frequency analysis of the ICG signal is carried out by integer filters on a sample by sample basis. They are simpler, lighter and more versatile when compared to the FFT. This alternative approach, although less accurate, is preferred due to the limited processing capacity of devices that could compromise real time usability of the FFT. These two techniques were compared across a data set comprising 13 cases of cardiac arrest and 6 normal controls. The best filters were refined on this training set and an algorithm for the detection of cardiac arrest was trained on a wider data set. The algorithm was finally tested on a validation set. The ICG was recorded in 132 cardiac arrest patients (53 training, 79 validation) and 97 controls (47 training, 50 validation): the diagnostic algorithm indicated cardiac arrest with a sensitivity of 81.1% (77.6-84.3) and specificity of 97.1% (96.7-97.4) for the validation set (95% confidence intervals). Automated defibrillators with integrated ICG analysis have the potential to improve emergency care by lay persons enabling more rapid and appropriate initiation of CPR and when combined with ECG analysis they could improve on the detection of cardiac arrest.

Further evidence consistent with Yqh as an indicator of risk of gonadal blastoma in Y-bearing mosaic Turner syndrome

An 8-year-old girl with some features of Turner syndrome and karyotype 45X/46XY had developed a bilateral gonadoblastoma in her rudimentary ovaries. Her normal Y chromosome showed the characteristic distal fluorescence, as seen in her father's. Another mosaic, this time 45X/46XidicY, and also with some Turner features had rudimentary ovaries, but no gonadoblastoma had developed at age 14. The nature of her idicY, which showed no fluorescent distal Yq and had one of the centromeres inactivated, was confirmed by in situ hybridisation with a Yp-specific probe. Using primers from a human Yp-specific sequence, we amplified DNA extracted from paraffin-embedded ovarian tissue from both cases, and from a normal testicle and a normal ovary as controls. The finding of the expected Y-derived PCR product in the rudimentary gonads from these mosaic patients indicates the presence of their Y chromosome in both. We discuss the validity of the findings, and the possible role of sequences in or near the fluorescent part of Yq in the origin of gonadoblastoma in Y-bearing mosaic Turner syndrome.