Collagen-coated vs noncoated low-weight polypropylene meshes in a sheep model for vaginal surgery. A pilot study

The aims of this study were dual. First, to evaluate the feasibility of a sheep model as an animal model for vaginal surgery with meshes. Second, to compare host response to two low-weight polypropylene (PP) meshes, a noncoated (Soft Prolene™, Gynecare, Ethicon) and a coated mesh with an absorbable hydrophilic film (Ugytex™, Sofradim). Thirty-six 20×20 mm polypropylene meshes (18 coated and 18 noncoated) were surgically implanted by the vaginal route in 12 adult ewes. Meshes were implanted in the anterior (n=12) and the posterior vaginal compartments (n=24). Animals were killed 1 (n=6) and 12 (n=6) weeks after surgery. Postimplantation evaluation included macroscopical examination, histological and immunohistochemical analysis and histomorphometrical measures of the distance between the meshes and the vaginal epithelium. The experimental procedure was feasible in all cases. Vaginal erosions were observed twice as frequently with the noncoated-PP meshes (6/18, 33.3%) as with the coated-PP meshes (3/18, 16.7%), even if that difference was not significant (p=0.4). However, no differences were observed between the two meshes in terms of shrinkage, tissue ingrowth, inflammatory response, and position of the mesh in the vaginal wall. The mechanism involved in the reduction of vaginal erosion could be due to the lesser adhesion of the coated mesh on the vaginal wound during the early postoperative period.     

Hepatic metabolism of colloidal gold-low-density lipoprotein complexes in the rat: evidence for bulk excretion of lysosomal contents into bile

Rats were treated with 17 alpha-ethinyl estradiol to induce high levels of low-density lipoprotein receptors in hepatocytes. When these rats were given intravenous injections of low-density lipoprotein-colloidal gold complexes, most of the gold (labeled with 195Au) appeared to be taken up by Kupffer cells, as were complexes of colloidal gold with albumin or polyvinylpyrrolidone. However, when these rats were also administered gadolinium chloride, which blocks Kupffer cell activity, most of the low-density lipoprotein-gold (but not gold complexed with albumin or polyvinylpyrrolidone) was taken up into hepatocytes by receptor-mediated endocytosis and concentrated in peribiliary lysosomes, as determined by electron microscopy. Colloidal gold taken up as a complex with low-density lipoprotein was excreted into the feces via the common bile duct at a maximal rate of about 5% daily, 4 to 12 days after injection. Thereafter, the rate of gold excretion fell off until reaching a plateau after 3 weeks. At this late time, most of the colloidal gold was shown by electron microscopy to be in Kupffer cells, whereas earlier (6 days after injection) it was contained mainly in older hepatocytic lysosomes, identified by lipofuscin granules. It is concluded that, in rats, hepatocytic lysosomes empty most of their contents into bile every week or two, apparently by exocytosis.     

Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study

Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity.     

Bacterial adaptation to the gut environment favors successful colonization: microbial and metabonomic characterization of a simplified microbiota mouse model

Rodent models harboring a simple yet functional human intestinal microbiota provide a valuable tool to study the relationships between mammals and their bacterial inhabitants. In this study, we aimed to develop a simplified gnotobiotic mouse model containing 10 easy-to-grow bacteria, readily available from culture repositories, and of known genome sequence, that overall reflect the dominant commensal bacterial makeup found in adult human feces. We observed that merely inoculating a mix of fresh bacterial cultures into ex-germ free mice did not guarantee a successful intestinal colonization of the entire bacterial set, as mice inoculated simultaneously with all strains only harbored 3 after 21 d. Therefore, several inoculation procedures were tested and levels of individual strains were quantified using molecular tools. Best results were obtained by inoculating single bacterial strains into individual animals followed by an interval of two weeks before allowing the animals to socialize to exchange their commensal microbes. Through this procedure, animals were colonized with almost the complete bacterial set (9/10). Differences in the intestinal composition were also reflected in the urine and plasma metabolic profiles, where changes in lipids, SCFA, and amino acids were observed. We conclude that adaptation of bacterial strains to the host's gut environment (mono-colonization) may predict a successful establishment of a more complex microbiota in rodents.     

Cardiac Micro-PET-CT

Molecular imaging is a rapidly emerging field, with the use of multi-modality or hybrid technology scanners for in vivo investigations covering a broad spectrum of disease. Cardiac micro-PET-CT is one such promising multimodality. Standalone imaging technologies such as PET and CT have existed for several decades, however, they have only recently been utilized in concert, mainly for clinical cancer imaging. Cardiovascular events are responsible for nearly one-third of deaths in North America every year. Atherosclerosis, coronary artery disease (CAD), and heart failure are the most common types of heart disease. Cardiac imaging-related research into their prevention and treatment has contributed to a decrease in mortality. This review outlines the recent progress in the development and application of advanced cardiac micro-PET-CT technology. Current development of novel PET radiotracers focusing on diagnosis and characterization of different stages of atherosclerosis is discussed, as well as myocardial perfusion radiotracers mimicking previously established SPECT tracers and others. Small animal (mouse and rat) models of disease investigated with cardiac imaging are becoming more common, and will facilitate rapid translation to clinical studies with improvement in micro-PET-CT technology. Also, increasingly popular animal models for cardiovascular disease research such as mini-pigs and rabbits are used with interventional therapies, including catheterization due to larger artery sizes. The emergence of cardiac CT will be discussed with comparison between preclinical and clinical approaches, including consideration of radiation doses.     

Sexual behaviors and their correlates among young people in Mauritius: a cross-sectional study

Background  

Little is known about the HIV/AIDS epidemic in the Indian Ocean region, including Mauritius. National records suggest a prevalence of HIV in Mauritius of < 1% in the general population, which is one of the lowest prevalence rates in southern Africa. However, HIV-positive cases have been increasing recently in Mauritius. We conducted a cross-sectional survey in January 2003 to assess the prevalence of HIVrelated sexual behaviors and their correlates among young people aged 15–24 years in Mauritius.     

Symptomatic treatment of pain in cervico-facial cancers]

Pain is frequent in patients presenting cervico-facial cancers. It can be acute or persistent, or present at the morbid entity known as chronic pain. The specific anatomical site and the often poor environment explain that the physical disability related to pain is increased by multiple psychosocial problems. Multidisciplinary care management by several actors is required and can be facilitated by a simple decision-making model. The schema presented can be used to prompt discussion and criticism. It needs constant improvement and extensions in order to reach a consensual attitude towards this king of suffering but also towards other situations of pain care management frequently encountered in cancer patients as well as those with other pathologies.     

Propofol differently alters vascular reactivity in normotensive and hypertensive rats

1. The effect of propofol on arterial tone in hypertension is poorly understood. We examined the effect of increasing concentrations of propofol (5.6 x 10-8 to 2.8 x 10-3 mol/L) on isometric tension developed by noradrenaline (10-7 mol/L)-contracted aortic rings from 12-week-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. In both WKY rats and SHR, propofol induced a dose-dependent inhibition of contraction induced by noradrenaline, but the amplitude of relaxation was larger in the SHR than in WKY rats. 3. The effects of propofol was endothelium independent in WKY rats, whereas in SHR relaxation induced by propofol was greater in endothelium-intact than in endothelium-denuded rings. 4. In conclusion, we found significant differences in the effect of propofol in hypertensive rats, which may be related to differences in structural and functional properties of the arterial wall observed in hypertension.     

The neurotensin receptor antagonist SR 142948A blocks the efflux of dopamine evoked in nucleus accumbens by neurotensin ejection into the ventral tegmental area

The neuropeptide neurotensin (NT) exerts a wide range of central and peripheral effects. In particular, ejection of NT (10(-7) M, 65 nl) into the ventral tegmental area (VTA) in anaesthetised rats pre-treated with pargyline increases the dopamine (DA) efflux within the nucleus accumbens (NAcc) as measured by differential pulse amperometry (DPA) combined with carbon fibre electrodes. However, this effect is not blocked by systemic pre-treatment with the potent and selective non-peptide NT receptor antagonists SR 48692 and SR 142948A, at any dose studied. The present study was designed to determine the ability of these NT receptor antagonists to block the increase in DA efflux evoked within the NAcc when they are locally applied with the peptide into the VTA. The competitive N-methyl- D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP-5), applied into the VTA 1 min before NMDA, blocked the effect of NMDA on DA efflux concentration and volume dependently, thus demonstrating the suitability of our experimental procedure for characterizing both an agonist and an antagonist specific for receptors present on mesencephalic dopaminergic neurons and involved in the regulation of DA efflux within the NAcc. Intra-VTA application of SR 142948A blocked the NT-evoked increase in DA efflux within the NAcc dose dependently whereas SR 48692, at the concentration used, was inactive. These results suggest that NT regulates mesencephalic dopaminergic activity through NT receptors sensitive to SR 142948A, but possibly not to SR 48692.