High resolution solid-state 29si nmr spectroscopy of silicone gels used to fill breast prostheses

We have used ²⁹Si solid-state nuclear magnetic resonance (NMR) spectroscopy to study the chemical structure of the silicone gels in virgin and explanted breast prostheses. Despite evidences of alteration in the morphological appearance of the silicone gel inside the breast prosthesis, our results do not reveal changes in the chemical nature and structure of the silicone gels after implantation. In addition to the main ²⁹Si resonance peak at ?22.26 ppm that corresponds to the resonance frequency of the D repeat unit of the polysiloxane chains, the high sensitivity of our NMR technique allows the detection of very low concentrations of silicone compounds. Within our experimental detection limit of 0.2%, no signal between ?90 ppm and ?150 ppm are observed. This indicates that no silica products are present inside the gel of the prostheses. Furthermore, our ²⁹Si NMR spectra indicate differences in the chemical compositions of the silicone gels from different manufacturers.     

Effects of methimazole pretreatment on cerulein induced acute pancreatitis in rats.

BACKGROUND: Many interrelationships exist between the thyroid gland and the gastrointestinal tract. Several past and recent studies have shown that the thyroid gland profoundly influences the structure and function of the exocrine pancreas in the rat. In the present study we investigated the effect of methimazole (METZ), an antithyroid drug, on cerulein induced acute pancreatitis (AP) in rats. METHODS: Rats were divided into 3 groups (10-12 weeks age, 200-250 g weight, n: 10). Group B was made hypothyroid with methimazole 5 mg/kg daily for 10 days and the others were untreated euthyroid groups. After 10 days, acute pancreatitis was induced with four doses of 20 microg/kg body weight of cerulein administered s.c at hourly intervals in group A and B while the control group C was given 4 doses of I ml saline. Pancreas wet weight (mg), plasma amylase activity (IU/l) and pancreatic histology were used as endpoints to quantify the severity of the AP. RESULTS: Plasma tri-iodothyronine (T3) (ng/dl) and thyroxine (T4) (microg/dl) levels were significantly reduced after METZ treatment for 10 days (p < 0.01). METZ pretreatment reduced significantly the cerulein induced increase in pancreatic weight (1,205 +/- 12 mg in METZ treated AP group versus 1,617 +/- 14 mg in AP group, p < 0.05) and the rise in amylase activity (7,078 +/- 816 IU/l in METZ treated AP group versus 8,611 +/- 830 IU/l in AP group p < 0.05). CONCLUSION: METZ reduces the severity of cerulein induced AP in rats. This effect might be through its antithyroid property.     

Effects of antisense mediated inhibition of cathepsin K on human osteoclasts obtained from peripheral blood.

Cathepsin K is a cystein protease that displays a proteolytic activity against Type I collagen and is abundantly and selectively expressed in osteoclasts where it plays a critical role in bone degradation. Its direct role in bone tissue has been defined by knock-out mice studies and inhibiting strategies in animals models. However, direct proof of cathepsin K function in human osteoclast model in vitro is lacking. The aim of this study is to analyze cathepsin K expression and localization in human osteoclasts obtained from peripheral blood and to examine cathepsin K function in these cells by antisense oligodeoxynucleotide (AS-ODN) strategy. AS-ODN was added to the culture of osteoclast precursors induced to differentiate by RANKL and M-CSF. AS-ODN treatment produced a significant down-regulation of cathepsin K mRNA (>80%) and protein expression, as verified respectively by Real-time PCR and by immunocytochemistry or Western blot. The cathepsin K inhibition caused an impairment of resorption activity as evaluated by a pit formation assay ( p = 0.045) and by electron microscopy, while the acidification process was unaffected. We demonstrated that antisense strategies against cathepsin K are selectively effective to inhibit resorption activity in human osteoclasts, like in animal models.     

The topologic and chronologic patterns of hematopoietic cell seeding in host femoral bone marrow after transplantation.

The early stages of homing, seeding, and engraftment of hematopoietic stem and progenitor cells are poorly characterized. We have developed an optical technique that allows in vivo tracking of transplanted, fluorescent-tagged cells in the host femurs. In this study we used fluorescence microscopy to monitor the topologic and chronologic patterns of hematopoietic cell seeding in the femoral bone marrow (BM) of mice. PKH-labeled cells homed to the femur within minutes after injection into a peripheral vein. Most cells drifted within the marrow space and gradually seeded in clusters close to the endosteal surface of the epiphyseal cortex. Three days after transplantation 85% to 94% (14%) of PKH-labeled cells in the femoral marrow were located within 100 microm of the epiphyseal bone surface (P <.001 versus the more central cells), whereas labeled cells were absent in the femoral diaphysis. Primary seeding of juxtaendosteal, epiphyseal marrow occurred independently of recipient conditioning (myeloablated and nonconditioned hosts), donor-recipient antigen disparity, or the phenotype of the injected cells (whole BM and lineage-negative cells) and was consistently observed in secondary recipients of BM-homed cells. Seeding in regions close to the epiphyseal bone was also observed in freshly excised femurs perfused ex vivo and in femurs assessed without prior placement of optical windows, indicating that the site of primary seeding was not affected by surgical placement of optical windows. Four to 5 days after transplantation, cellular clusters appeared in the more central regions of the epiphyses and in the diaphyses. Centrally located cells showed decreased PKH fluorescence, suggesting that they were progeny of the seeding cells, and brightly fluorescent cells (quiescent first-generation seeding cells) were observed close to the bone surface for as long as 24 days after transplantation. These data indicate that the periphery of the femoral marrow hosts primary seeding and that quiescent cells continue to reside in the periphery for weeks and do not divide. The site of proliferation of transplanted cells is the center of the marrow space.     

Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.     

Methimazole Slows Hepatocyte Streaming in Rats

Hepatocytes are hypothesized to continuallystream from the portal tract to the terminal hepaticvein. By this model, when a cell divides, one of itsprogeny replaces the dividing ancestor and the other is displaced into a more remote location. Thepresent experiment aims to demonstrate thathypothyroidism affects liver cell turnover. Thirty maleadult rats were divided into two groups. One receivedmethimazole for two weeks and the other served as control.Each rat was injected intraperitoneally with 18.5 KBq[³H]thymidine/g body weight. Rats were killedafter 1 hr and two and four weeks. Autoradiography was done. The distance of the labeled cells fromthe portal tract was measured. The mean TSH levels ofthe methimazole-treated group and controls were 1.45 and0.25 mM/liter, respectively (P < 0.01). Hepatocyte streaming was lower in hypothyroid (1.8m/day) than in untreated rats (2.5 m/day) (P< 0.01). The respective labeling indices 1 hr afterlabeling were 0.9% and 1.24% (P < 0.05). We concludethat hypothyroidism diminishes hepatocyte and littoral cellturnover and slows down their streaming.     

Impedance cardiographic monitoring during pericardiocentesis: comparison with echocardiography

OBJECTIVE: Thoracic impedance cardiography (TIC) is a noninvasive method which has proved to be useful in monitoring the haemodynamic status of the patients. In this study, we evaluated the TIC findings in patients with pericardial effusion and cardiac tamponade. METHODS AND RESULTS: The study consisted of patients with pericardial effusion with (group A) or without (group B) cardiac tamponade (CT). The stroke volume, cardiac output and ejection fraction was measured by both echocardiography and TIC. The measurements were done at baseline in both groups and following pericardiocentesis in group A. The variables were compared by linear regression analysis, paired sample's t test and chi-square test. The study included 32 patients. Group A consisted of 16 patients and group B of 14 patients. Two patients were excluded from comparisons because of insufficient quality of the echocardiographic examination. There were no significant differences between group A and B with regard to demographic features. Both echocardiographic and TIC measurements at baseline revealed decreased cardiac output, EDV and SV in group A and EF was not different. Linear regression analysis revealed that echocardiography and TIC were in significant correlation with regard to cardiac output, enddiastolic volume, stroke volume (p < 0.01) but not ejection fraction (p = 0.8910). The correlation was also present after pericardiocentesis. CONCLUSIONS: TIC can be safely used in patients with pericardial effusion. It provides suggestive data for the diagnosis of CT and can be used as a means of monitoring the results of the pericardiocentesis.