Experimental evaluation of an electromechanical artificial urinary sphincter in an animal model.

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The AMS 800 urinary control system is the gold standard for the treatment of urinary incontinence due to sphincter insufficiency. Despite excellent functional outcome and latest technological improvements, the revision rate remains significant. To overcome the shortcomings of the current device, we developed a modern electromechanical artificial urinary sphincter. The results demonstrated that this new sphincter is effective and well tolerated up to 3 months. This preliminary study represents a first step in the clinical application of novel technologies and an alternative compression mechanism to the urethra. OBJECTIVES: To evaluate the effectiveness in continence achievement of a new electromechanical artificial urinary sphincter (emAUS) in an animal model. To assess urethral response and animal general response to short-term and mid-term activation of the emAUS. MATERIALS AND METHODS: The principle of the emAUS is electromechanical induction of alternating compression of successive segments of the urethra by a series of cuffs activated by artificial muscles. Between February 2009 and May 2010 the emAUS was implanted in 17 sheep divided into three groups. The first phase aimed to measure bladder leak point pressure during the activation of the device. The second and third phases aimed to assess tissue response to the presence of the device after 2-9 weeks and after 3 months respectively. Histopathological and immunohistochemistry evaluation of the urethra was performed. RESULTS: Bladder leak point pressure was measured at levels between 1091 ± 30.6 cmH2 O and 1244.1 ± 99 cmH2 O (mean ± standard deviation) depending on the number of cuffs used. At gross examination, the explanted urethra showed no sign of infection, atrophy or stricture. On microscopic examination no significant difference in structure was found between urethral structure surrounded by a cuff and control urethra. In the peripheral tissues, the implanted material elicited a chronic foreign body reaction. Apart from one case, specimens did not show significant presence of lymphocytes, polymorphonuclear leucocytes, necrosis or cell degeneration. Immunohistochemistry confirmed the absence of macrophages in the samples. CONCLUSIONS: This animal study shows that the emAUS can provide continence. This new electronic controlled sequential alternating compression mechanism can avoid damage to urethral vascularity, at least up to 3 months after implantation. After this positive proof of concept, long-term studies are needed before clinical application could be considered.

Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet.

OBJECTIVE-Obesity and associated pathologies are major global health problems. Transforming growth factor-beta/Smad3 signaling has been implicated in various metabolic processes, including adipogenesis, insulin expression, and pancreatic beta-cell function. However, the systemic effects of Smad3 deficiency on adiposity and insulin resistance in vivo remain elusive. This study investigated the effects of Smad3 deficiency on whole-body glucose and lipid homeostasis and its contribution to the development of obesity and type 2 diabetes.RESEARCH DESIGN AND METHODS-We compared various metabolic profiles of Smad3-knockout and wild-type mice. We also determined the mechanism by which Smad3 deficiency affects the expression of genes involved in adipogenesis and metabolism. Mice were then challenged with a high-fat diet to study the impact of Smad3 deficiency on the development of obesity and insulin resistance.RESULTS-Smad3-knockout mice exhibited diminished adiposity with improved glucose tolerance and insulin sensitivity. Chromatin immunoprecipitation assay revealed that Smad3 deficiency increased CCAAT/enhancer-binding protein beta-C/EBP homologous protein 10 interaction and exerted a differential regulation on proliferator-activated receptor beta/delta and proliferator-activated receptor gamma expression in adipocytes. Focused gene expression profiling revealed an altered expression of genes involved in adipogenesis, lipid accumulation, and fatty acid beta-oxidation, indicative of altered adipose physiology. Despite reduced physical activity with no modification in food intake, these mutant mice were resistant to obesity and insulin resistance induced by a high-fat diet.CONCLUSIONS-Smad3 is a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes, suggesting that Smad3 may be a potential target for the treatment of obesity and its associated disorders.

Optimal 3-T MRI for depiction of the finger A2 pulley: comparison between T1-weighted, fat-saturated T2-weighted and gadolinium-enhanced fat-saturated T1-weighted sequences

OBJECTIVE: To compare three spin-echo sequences, transverse T1-weighted (T1WI), transverse fat-saturated (FS) T2-weighted (T2WI), and transverse gadolinium-enhanced (Gd) FS T1WI, for the visualisation of normal and abnormal finger A2 pulley with magnetic resonance (MR) imaging at 3 tesla (T). MATERIALS AND METHODS: Sixty-three fingers from 21 patients were consecutively investigated. Two musculoskeletal radiologists retrospectively compared all sequences to assess the visibility of normal and abnormal A2 pulleys and the presence of motion or ghost artefacts. RESULTS: Normal and abnormal A2 pulleys were visible in 94% (59/63) and 95% (60/63) on T1WI sequences, in 63% (40/63) and 60% (38/63) on FS T2WI sequences, and in 87% (55/63) and 73% (46/63) on Gd FS T1WI sequences when read by the first and second observer, respectively. Motion and ghost artefacts were higher on FS T2WI sequences. Seven among eight abnormal A2 pulleys were detected, and were best depicted with Gd FS T1WI sequences in 71% (5/7) and 86% (6/7) by the first and the second observer, respectively. CONCLUSION: In 3-T MRI, the comparison between transverse T1WI, FS T2WI, and Gd FS T1WI sequences shows that transverse T1WI allows excellent depiction of the A2 pulley, that FS T2WI suffers from a higher rate of motion and ghost artefacts, and transverse Gd FS T1WI is the best sequence for the depiction of abnormal A2 pulley.

Differences in whole-body fat oxidation kinetics between cycling and running.

This study aimed to quantitatively describe and compare whole-body fat oxidation kinetics in cycling and running using a sinusoidal mathematical model (SIN). Thirteen moderately trained individuals (7 men and 6 women) performed two graded exercise tests, with 3-min stages and 1 km h(-1) (or 20 W) increment, on a treadmill and on a cycle ergometer. Fat oxidation rates were determined using indirect calorimetry and plotted as a function of exercise intensity. The SIN model, which includes three independent variables (dilatation, symmetry and translation) that account for main quantitative characteristics of kinetics, provided a mathematical description of fat oxidation kinetics and allowed for determination of the intensity (Fat(max)) that elicits maximal fat oxidation (MFO). While the mean fat oxidation kinetics in cycling formed a symmetric parabolic curve, the mean kinetics during running was characterized by a greater dilatation (i.e., widening of the curve, P < 0.001) and a rightward asymmetry (i.e., shift of the peak of the curve to higher intensities, P = 0.01). Fat(max) was significantly higher in running compared with cycling (P < 0.001), whereas MFO was not significantly different between modes of exercise (P = 0.36). This study showed that the whole-body fat oxidation kinetics during running was characterized by a greater dilatation and a rightward asymmetry compared with cycling. The greater dilatation may be mainly related to the larger muscle mass involved in running while the rightward asymmetry may be induced by the specific type of muscle contraction.

Determinants of basal fat oxidation in healthy Caucasians.

In a retrospective study, we examined several determinants of basal fat oxidation in 720 healthy Caucasian volunteers. Adult men (n = 427) and women (n = 293) were characterized for resting energy expenditure and substrate oxidation by indirect calorimetry (after a 12-h overnight fast), peak O2 consumption by a treadmill test to exhaustion, body composition by hydrodensitometry, food intake from a 3-day food diary, and hormonal status by fasting hormone concentrations. Fat oxidation was negatively correlated with fat mass in men (r = -0.11; P < 0.05), but no statistical relationship was found in women. In a stepwise multiple regression analysis, fat oxidation was best predicted by peak O2 consumption and fat-free mass in men (model R2 = 0.142) and by free thyroxine, fat-free mass, and fasting insulin in women (model R2 = 0.153). Relative rates of fat oxidation (fat oxidation adjusted for differences in resting energy expenditure) were not correlated with fat mass in either gender. Women showed a lower rate of basal fat oxidation (both absolute and adjusted) than did men. Our results show that fat oxidation is not greater in individuals with a greater fat mass. Furthermore, our results support a sexual dimorphism in basal rates of fat oxidation.

Development of a coculture model of encapsulated cells.

In the whole animal, metabolic regulations are set by reciprocal interactions between various organs, via the blood circulation. At present, analyses of such interactions require numerous and uneasily controlled in vivo experiments. In a search for an alternative to in vivo experiments, our work aims at developing a coculture system in which different cell types are isolated in polymer capsules and grown in a common environment. The signals exchanged between cells from various origins are, thus, reproducing the in vivo intertissular communications. With this perspective, we evaluated a new encapsulation system as an artificial housing for liver cells on the one hand and adipocytes on the other hand. Murine hepatocytes were encapsulated with specially designed multicomponent capsules formed by polyelectrolyte complexation between sodium alginate, cellulose sulphate and poly(methylene-coguanidine) hydrochloride, of which the permeability has been characterized. We demonstrated the absence of cytotoxicity and the excellent biocompatibility of these capsules towards primary culture of murine hepatocytes. Encapsulated hepatocytes retain their specific functions--transaminase activity, urea synthesis, and protein secretion--during the first four days of culture in minimum medium. Mature adipocytes, isolated from mouse epidydimal fat, were embedded in alginate beads. Measurement of protein secretion shows an identical profile between free and embedded adipocytes. We finally assessed the properties of encapsulated hepatocytes, cryopreserved over a periods of up to four months. The perspective of using encapsulated cells in coculture are discussed, since this system may represent a promising tool for fundamental research, such as analyses of drug metabolism, intercellular regulations, and metabolic pathways, as well as for the establishment of a tissue bank for storage and supply of murine hepatocytes.

Avian erythrocytes have functional mitochondria, opening novel perspectives for birds as animal models in the study of ageing.

BACKGROUND: In contrast to mammalian erythrocytes, which have lost their nucleus and mitochondria during maturation, the erythrocytes of almost all other vertebrate species are nucleated throughout their lifespan. Little research has been done however to test for the presence and functionality of mitochondria in these cells, especially for birds. Here, we investigated those two points in erythrocytes of one common avian model: the zebra finch (Taeniopygia guttata). RESULTS: Transmission electron microscopy showed the presence of mitochondria in erythrocytes of this small passerine bird, especially after removal of haemoglobin interferences. High-resolution respirometry revealed increased or decreased rates of oxygen consumption by erythrocytes in response to the addition of respiratory chain substrates or inhibitors, respectively. Fluorometric assays confirmed the production of mitochondrial superoxide by avian erythrocytes. Interestingly, measurements of plasmatic oxidative markers indicated lower oxidative stress in blood of the zebra finch compared to a size-matched mammalian model, the mouse. CONCLUSIONS: Altogether, those findings demonstrate that avian erythrocytes possess functional mitochondria in terms of respiratory activities and reactive oxygen species (ROS) production. Interestingly, since blood oxidative stress was lower for our avian model compared to a size-matched mammalian, our results also challenge the idea that mitochondrial ROS production could have been one actor leading to this loss during the course of evolution. Opportunities to assess mitochondrial functioning in avian erythrocytes open new perspectives in the use of birds as models for longitudinal studies of ageing via lifelong blood sampling of the same subjects.

Biometal muscle to restore atrial transport function in a permanent atrial fibrillation animal model: a potential tool in the treatment of end-stage heart failure.

BACKGROUND: Half of the patients with end-stage heart failure suffer from persistent atrial fibrillation (AF). Atrial kick (AK) accounts for 10-15% of the ejection fraction. A device restoring AK should significantly improve cardiac output (CO) and possibly delay ventricular assist device (VAD) implantation. This study has been designed to assess the mechanical effects of a motorless pump on the right chambers of the heart in an animal model. METHODS: Atripump is a dome-shaped biometal actuator electrically driven by a pacemaker-like control unit. In eight sheep, the device was sutured onto the right atrium (RA). AF was simulated with rapid atrial pacing. RA ejection fraction (EF) was assessed with intracardiac ultrasound (ICUS) in baseline, AF and assisted-AF status. In two animals, the pump was left in place for 4 weeks and then explanted. Histology examination was carried out. The mean values for single measurement per animal with +/-SD were analysed. RESULTS: The contraction rate of the device was 60 per min. RA EF was 41% in baseline, 7% in AF and 21% in assisted-AF conditions. CO was 7+/-0.5 l min(-1) in baseline, 6.2+/-0.5 l min(-1) in AF and 6.7+/-0.5 l min(-1) in assisted-AF status (p<0.01). Histology of the atrium in the chronic group showed chronic tissue inflammation and no sign of tissue necrosis. CONCLUSIONS: The artificial muscle restores the AK and improves CO. In patients with end-stage cardiac failure and permanent AF, if implanted on both sides, it would improve CO and possibly delay or even avoid complex surgical treatment such as VAD implantation.

Fat intake and adiposity in 8 to 11-year-old obese children.

OBJECTIVE: To investigate the relationships between diet composition, body composition, and macronutrient oxidation at rest in obese and non-obese children. DESIGN: Cross-sectional study on fat intake, adiposity and postabsorptive macronutrients oxidation rates. SUBJECTS: 82 prepubertal (age: 9.1 +/- 1.1 y) children, 30 obese (FM = 32.6 +/- 6.1%) and 52 non-obese (FM = 15.6 +/- 5.1%). MEASUREMENTS: Subcutaneous skinfold thickness for body composition, diet history for energy and nutrient intake, indirect calorimetry for resting metabolic rate (RMR) and RQ measurement. RESULTS: Energy intake (EI) was comparable in obese and non-obese children. Adjusted for RMR by ANCOVA, using RMR as the covariate, EI was significantly lower in obese than in non-obese children indicating either a blunted physical activity or a systematic underestimation of EI. Protein and carbohydrate intakes expressed as a percentage of total energy intake (%EI) were not significantly different in the two groups. Lipid intake (%EI) was slightly but significantly higher in the obese than in the non-obese group either unadjusted or adjusted for RMR by ANCOVA. The postabsorptive RQ was significantly lower in obese than in non-obese children. In the total group, %FM was weakly but significantly correlated to lipid intake (%EI). CONCLUSION: Obese prepubertal children have a higher relative fat intake than non-obese children and their FM is associated with this factor. The lower postabsorptive RQ of obese children may indicate a compensatory mechanism to achieve fat equilibrium by enhanced fat oxidation.

Reproducibility and within-day variability of body fat measurements using segmental bipolar bioelectrical impedance in women

BACKGROUND AND AIMS: little is known regarding the reproducibility of body fat measuring devices; hence, we assessed the between and within-device reproducibility, and the within-day variability of body fat measurements. METHODS: body fat percentage was measured twice on seventeen female students aged between 18 and 20 with a body mass index of 21.9 ± 2.5 kg/m2 (mean ± SD) using seven bipolar bioelectrical impedance devices. Each participant was also measured each hour between 7:00 and 22:00. RESULTS: the correlation between first and second measurements was very high (Spearman r between 0.985 and 1.000, p<0.001), as well as between devices (Spearman r between 0.916 and 0.991, p<0.001). Repeated measurements analysis showed no differences were between devices (p=0.59) or readings (first vs. second: p=0.74). Conversely, significant differences were found between assessment periods throughout the day, measurements made in the morning being lower than those made in the afternoon (F test for repeated values= 6.58, p<0.001). CONCLUSIONS: the between and within-device reproducibility for measuring body fat is high, enabling the use of multiple devices in a single study. Conversely, small but significant changes in body fat measurements occur during the day, urging body fat measurements to be performed at fixed times.

Techniques of DNA-studies on prehispanic ectoparasites (Pulex sp., Pulicidae, Siphonaptera) from animal mummies of the Chiribaya Culture, Southern Peru

During a paleoparasitological survey of several animal mummies (Cavia aperea f. porcellus and Canis familiaris) from Chiribaya Baja, an archaeological site in Southern Peru, an unexpected find was made. In the well preserved fur, large numbers of mummified fleas (Pulex simulans/irritans)that parasitized the animals during life were encountered. Due to the relative recent event of the host mummification and the outstanding preservation of the fleas, an attempt for the retrieval of DNA was made. A DNA extraction and sequencing protocol for archaeological ectoparasitic remains has been established, taking additional studies for tissue and protein preservation into account. Tissue preservation was assessed with transmission electron microscopy and the protein preservation was tested through the racemisation ratios of aspartic acid. Regions of the 28S rDNA gene were successfully amplified and sequenced. Further research perspectives are outlined.

Molluscicidal effect of nicotinanilide and its intermediate compounds against a freshwater snail Lymnaea luteola, the vector of animal schistosomiasis

The molluscicidal effect of nicotinanilide was evaluated and compared with niclosamide (2',5-dichloro-4'-nitrosalicylanilide, ethanolamide salt) against different stages of the freshwater snail Lymnaea luteola i.e., eggs, immature, young mature, and adults. Calculated values of lethal concentrations (LC50 and LC90 ) showed that both nicotinanilide and niclosamide as toxic against eggs, immature, and adults. The young mature stage of the snails was comparatively more tolerant to both molluscicides than the other stages. The toxicity of the intermediate compounds of nicotinanilide against the young mature stage of the snails showed them as ineffective. The mortality pattern of the snails exposed to LC90 concentration of these molluscicides showed niclosamide to kill faster (within 8 to 9 h) than nicotinanilide (26 to 28 h). In view of the above studies it may be concluded that both molluscicides are toxic against all the stages of the L. luteola snails.