Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques

Abstract Background Mature carotid plaques are complex structures, and their histological classification is challenging. The carotid plaques of asymptomatic and symptomatic patients could exhibit identical histological components. Objectives To investigate whether matrix metalloproteinase 9 (MMP-9), tissue inhibitor of MMP (TIMP), and cyclooxygenase-2 (COX-2) have different expression levels in advanced symptomatic carotid plaques, asymptomatic carotid plaques, and normal tissue. Methods Thirty patients admitted for carotid endarterectomy were selected. Each patient was assigned preoperatively to one of two groups: group I consisted of symptomatic patients (n = 16, 12 males, mean age 66.7 ± 6.8 years), and group II consisted of asymptomatic patients (n = 14, 8 males, mean age 67.6 ± 6.81 years). Nine normal carotid arteries were used as control. Tissue specimens were analyzed for fibromuscular, lipid and calcium contents. The expressions of MMP-9, TIMP-1 and COX-2 in each plaque were quantified. Results Fifty-eight percent of all carotid plaques were classified as Type VI according to the American Heart Association Committee on Vascular Lesions. The control carotid arteries all were classified as Type III. The median percentage of fibromuscular tissue was significantly greater in group II compared to group I (p < 0.05). The median percentage of lipid tissue had a tendency to be greater in group I than in group II (p = 0.057). The percentages of calcification were similar among the two groups. MMP-9 protein expression levels were significantly higher in group II and in the control group when compared with group I (p < 0.001). TIMP-1 expression levels were significantly higher in the control group and in group II when compared to group I, with statistical difference between control group and group I (p = 0.010). COX-2 expression levels did not differ among groups. There was no statistical correlation between MMP-9, COX-2, and TIMP-1 levels and fibrous tissue. Conclusions MMP-9 and TIMP-1 are present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. When sections of a plaque are analyzed without preselection, MMP-9 concentration is higher in normal tissues and asymptomatic surgical specimens than in symptomatic specimens, and TIMP-1 concentration is higher in normal tissue than in symptomatic specimens.

Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus

The purpose of this study was to assess the expression profile of genes with potential role in the development of insulin resistance (adipokines, cytokines/chemokines, estrogen receptors) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placenta of pregnant women with gestational diabetes mellitus (GDM) and age-matched women with physiological pregnancy at the time of Caesarean section. qRT-PCR was used for expression analysis of the studied genes. Leptin gene expression in VAT of GDM group was significantly higher relative to control group. Gene expressions of interleukin-6 and interleukin-8 were significantly increased, whereas the expressions of genes for estrogen receptors alpha and beta were significantly reduced in SAT of GDM group relative to controls, respectively. We found no significant differences in the expression of any genes of interest (LEP, RETN, ADIPOR1, ADIPOR2, TNF-alpha, CD68, IL-6, IL-8, ER alpha, ER beta) in placentas of women with GDM relative to controls. We conclude that increased expression of leptin in visceral adipose depot together with increased expressions of proinflammatory cytokines and reduced expressions of estrogen receptors in subcutaneous fat may play a role in the etiopathogenesis of GDM.

Early fish oil supplementation and organ failure in patients with septic shock from abdominal infections: a propensity-matched cohort study

Fish oil (FO) has immunomodulating effects and may improve organ function and outcome in critically ill patients. This retrospective, propensity-matched cohort study investigates the effects of early intravenous FO supplementation on organ failure in patients with septic shock from abdominal infection.

Organ transplantation in Switzerland: impact of the new transplant law on cold ischaemia time and organ transports

On 1 July 2007 a new transplant law came into force in Switzerland. The principal item of this new law is the change from centre-oriented allocation to patient-oriented national allocation of organs. The aim of the present study is to assess the impact on cold ischaemia time (CIT) and transport requirements.

A navigation system for percutaneous needle interventions based on PET/CT images: design, workflow and error analysis of soft tissue and bone punctures

Percutaneous needle intervention based on PET/CT images is effective, but exposes the patient to unnecessary radiation due to the increased number of CT scans required. Computer assisted intervention can reduce the number of scans, but requires handling, matching and visualization of two different datasets. While one dataset is used for target definition according to metabolism, the other is used for instrument guidance according to anatomical structures. No navigation systems capable of handling such data and performing PET/CT image-based procedures while following clinically approved protocols for oncologic percutaneous interventions are available. The need for such systems is emphasized in scenarios where the target can be located in different types of tissue such as bone and soft tissue. These two tissues require different clinical protocols for puncturing and may therefore give rise to different problems during the navigated intervention. Studies comparing the performance of navigated needle interventions targeting lesions located in these two types of tissue are not often found in the literature. Hence, this paper presents an optical navigation system for percutaneous needle interventions based on PET/CT images. The system provides viewers for guiding the physician to the target with real-time visualization of PET/CT datasets, and is able to handle targets located in both bone and soft tissue. The navigation system and the required clinical workflow were designed taking into consideration clinical protocols and requirements, and the system is thus operable by a single person, even during transition to the sterile phase. Both the system and the workflow were evaluated in an initial set of experiments simulating 41 lesions (23 located in bone tissue and 18 in soft tissue) in swine cadavers. We also measured and decomposed the overall system error into distinct error sources, which allowed for the identification of particularities involved in the process as well as highlighting the differences between bone and soft tissue punctures. An overall average error of 4.23 mm and 3.07 mm for bone and soft tissue punctures, respectively, demonstrated the feasibility of using this system for such interventions. The proposed system workflow was shown to be effective in separating the preparation from the sterile phase, as well as in keeping the system manageable by a single operator. Among the distinct sources of error, the user error based on the system accuracy (defined as the distance from the planned target to the actual needle tip) appeared to be the most significant. Bone punctures showed higher user error, whereas soft tissue punctures showed higher tissue deformation error.

Coordinated gene expression in adipose tissue and liver differs between cows with high or low NEFA concentrations in early lactation

Dairy cows with high and low plasma non-esterified fatty acid (NEFA) concentrations in early lactation were compared for plasma parameters and mRNA expression of genes in liver and subcutaneous adipose tissue. The study involved 16 multiparous dairy cows with a plasma NEFA concentration of >500 mumol/l [n = 8, high NEFA (HNEFA)] and <140 mumol/l [n = 8, low NEFA (LNEFA)] in the first week post-partum (pp). Blood samples, adipose and liver tissues were collected on day 1 (+1d) and at week 3 pp (+3wk). Blood plasma was assayed for concentrations of metabolites and hormones. Subcutaneous adipose and liver tissues were analysed for mRNA abundance by real-time qRT-PCR encoding parameters related to lipid metabolism. Results showed that mean daily milk yield and milk fat quantity were higher in HNEFA than in LNEFA cows (p < 0.01), and the NEB was more negative in HNEFA than in LNEFA in +3wk too (p < 0.05). HNEFA cows had slightly lower (p < 0.1) insulin concentrations than LNEFA cows across the study period, and the body condition score decreased more from +1d to +3wk in HNEFA than in LNEFA (p = 0.09). The mRNA abundance of genes in the liver related to fatty acid oxidation (carnitine palmitoyltransferase 2 and very long chain acyl-coenzyme A dehydrogenase) and ketogenesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2) were lower in HNEFA than in LNEFA cows. No differences between the two groups were observed for mRNA expression of genes in adipose tissue. The number of calculated significant correlation coefficients (moderately strong) between parameters in the liver and in adipose tissue was nearly similar on +1d, and higher for HNEFA compared with LNEFA cows in +3wk. In conclusion, dairy cows with high compared with low plasma NEFA concentrations in early lactation show differentially synchronized mRNA expression of genes in adipose tissue and liver in +3wk that suggests a different orchestrated homeorhetic regulation of lipid metabolism.

A novel quantitative method for analyzing the distributions of nanoparticles between different tissue and intracellular compartments

The penetration, translocation, and distribution of ultrafine and nanoparticles in tissues and cells are challenging issues in aerosol research. This article describes a set of novel quantitative microscopic methods for evaluating particle distributions within sectional images of tissues and cells by addressing the following questions: (1) is the observed distribution of particles between spatial compartments random? (2) Which compartments are preferentially targeted by particles? and (3) Does the observed particle distribution shift between different experimental groups? Each of these questions can be addressed by testing an appropriate null hypothesis. The methods all require observed particle distributions to be estimated by counting the number of particles associated with each defined compartment. For studying preferential labeling of compartments, the size of each of the compartments must also be estimated by counting the number of points of a randomly superimposed test grid that hit the different compartments. The latter provides information about the particle distribution that would be expected if the particles were randomly distributed, that is, the expected number of particles. From these data, we can calculate a relative deposition index (RDI) by dividing the observed number of particles by the expected number of particles. The RDI indicates whether the observed number of particles corresponds to that predicted solely by compartment size (for which RDI = 1). Within one group, the observed and expected particle distributions are compared by chi-squared analysis. The total chi-squared value indicates whether an observed distribution is random. If not, the partial chi-squared values help to identify those compartments that are preferential targets of the particles (RDI > 1). Particle distributions between different groups can be compared in a similar way by contingency table analysis. We first describe the preconditions and the way to implement these methods, then provide three worked examples, and finally discuss the advantages, pitfalls, and limitations of this method.

[Integration process and organ-related fantasies in patients undergoing organ transplantation]

This review deals with an important aspect of organ transplantation, namely the process of psychic organ integration and organ-related fantasies. The body schema and body self are two important concepts in the integration of a transplanted organ. Different models and theories on organ integration are presented and will be discussed. There is evidence that beside the emotional impact and the influence on well-being, organ integration depends closely on psychic processes involving in the incorporation of the transplanted organ and the respective organ-related fantasies. Therefore, these organ fantasies - whether unconscious or conscious - may play an important role in the future development of the instinctive and highly individual relation the patients elaborate with the new organ. Beside the concern with the new organ, a bereavement to the lost old and sick organ may also influence the patients thoughts. Moreover, the good resolving of all these issues evokes the "good practice" patients develop towards the new situation. This will bring up issues as compliance, infections, rejection episodes and - most important - also organ survival.

Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

BACKGROUND: To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking. METHODS: From 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT) was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU) was 29 months. RESULTS: Acute and maximal late grade 2 gastrointestinal (GI) toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU) morbidity (PGUM) was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late > or = grade 2 GU toxicity free survival was associated with higher age (P = .025), absence of HT (P = .016) and higher PGUM (P < .001). DISCUSSION: GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

Sexual and organ function in patients with symptomatic prolapse: are pessaries helpful?

OBJECTIVE: To evaluate quality of life and pelvic organ and sexual function before and during pessary use in patients with symptomatic pelvic organ prolapse and to determine reasons which lead to cessation of pessary use. DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENT(S): Patients with symptomatic stage II or more prolapse of the anterior, posterior, or apical vaginal wall with or without uterus were included in this study. INTERVENTION(S): We used the Female Sexual Function Index questionnaire and the Sheffield prolapse questionnaire. For quality of life we used the King's Health Questionnaire. MAIN OUTCOME MEASURE(S): Main outcome measures were quality of life and sexual and pelvic organ function. RESULT(S): A total of 73 women participated in this study; 31 were sexually active. Desire, lubrication, and sexual satisfaction showed statistically significant improvement, and orgasm remained unchanged. Statistically significant improvement in the feeling of bulge occurred during therapy, stool outlet problems were significantly improved, overactive bladder symptoms were significantly better, and pessaries did not significantly alter incontinence. CONCLUSION(S): Pessaries have been shown to be a viable noninvasive treatment for pelvic organ prolapse improving organ and sexual function as well as general wellbeing.

Desertification mitigation and water harvesting based on sustainable land management

Traditionally, desertification research has focused on degradation assessments, whereas prevention and mitigation strategies have not sufficiently been emphasised, although the concept of sustainable land management (SLM) is increasingly being acknowledged. SLM strategies are interventions at the local to regional scale aiming at increasing productivity, protecting the natural resource base, and improving livelihoods. The global WOCAT initiative and its partners have developed harmonized frameworks to compile, evaluate and analyse the impact of SLM practices around the globe. Recent studies within the EU research project DESIRE developed a methodological framework that combines a collective learning and decision-making approach with use of best practices from the WOCAT database. In-depth assessment of 30 technologies and 8 approaches from 17 desertification sites enabled an evaluation of how SLM addresses prevalent dryland threats such as water scarcity, soil and vegetation degradation, low production, climate change, resource use conflicts and migration. Among the impacts attributed to the documented technologies, those mentioned most were diversified and enhanced production and better management of water and soil degradation, whether through water harvesting, improving soil moisture, or reducing runoff. Water harvesting offers under-exploited opportunities for the drylands and the predominantly rainfed farming systems of the developing world. Recently compiled guidelines introduce the concepts behind water harvesting and propose a harmonised classification system, followed by an assessment of suitability, adoption and up-scaling of practices. Case studies go from large-scale floodwater spreading that make alluvial plains cultivable, to systems that boost cereal production in small farms, as well as practices that collect and store water from household compounds. Once contextualized and set in appropriate institutional frameworks, they can form part of an overall adaptation strategy for land users. More field research is needed to reinforce expert assessments of SLM impacts and provide the necessary evidence-based rationale for investing in SLM. This includes developing methods to quantify and value ecosystem services, both on-site and off-site, and assess the resilience of SLM practices, as currently aimed at within the new EU CASCADE project.

Glucose transporter expression in eutopic endometrial tissue and ectopic endometriotic lesions

Endometriosis is an extremely prevalent disorder characterized by the growth of endometrial tissue at ectopic locations. Glycolysis is an energy-producing mechanism that occurs in almost all cells and requires an adequate uptake of glucose mediated by glucose transporter (GLUT) proteins. At present, however, very little is known about their expression in either the endometrium or the endometriotic lesions. The objective of this study was to examine the expression of SLC2A genes in the endometrium of women with and without endometriosis and in the matching ectopic tissue, and to confirm the presence of the GLUT proteins in ectopic lesions. There was a significantly higher expression of SLC2A3 and a significantly lower expression of SLC2A4 in women with endometriosis compared with those without. In women with endometriosis, the ectopic expression of SLC2A3, SLC2A4 and SLC2A5 was significantly higher than that observed in the matching eutopic tissue. GLUT1 protein expression was present in both epithelial and stromal cells and GLUT3 was confined to CD45-positive leukocytes. GLUT4 expression was strong in both ectopic epithelial and stromal cells and localized to the cellular membrane in epithelial cells. These results show that GLUT expression is altered between eutopic and ectopic tissue and between women with and without endometriosis, and that GLUT4 may represent a significant entry route for glucose into the endometriotic epithelial cells. The inducible nature of GLUT4 and its limited cellular expression may make GLUT4 an attractive target for non-hormone-based treatments of endometriosis.

Thrombosis during pregnancy: Risks, prevention, and treatment for mother and fetus--harvesting the power of omic technology, biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis

Maternal thromboembolism and a spectrum of placenta-mediated complications including the pre-eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. "Omic" technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non-invasive imaging technologies of the utero-placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non-cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases.