The protective effect of FK506 pretreatment against renal ischemia/reperfusion injury in rats

The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R) injury was investigated using a rat model. Animals were assigned to one of two groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while group 2 animals received FK506 (0.3 mg/kg), administered intravenously 24 hr prior to the induction of renal ischemia. A 60-min period of ischemia of the right kidney was induced, and upon reperfusion a left nephrectomy was performed. Blood samples for estimation of BUN, creatinine, and tumor necrosis factor were collected on days 0 (preischemia), 1, 2, 3, 5, 7, and 10 (postischemia). Rats were sacrificed after day 10 and renal tissue was examined histologically. All animals survived the ischemic episode. FK506 pretreatment significantly reduced the serum levels of BUN (P<0.02), creatinine (P<0.02), and TNF (P<0.05) as compared with that seen in controls. Histologically, at day 10, the kidneys showed the expected sequelae of prior renal I/R with various degrees of tubular damage. However, no objective differences were evident between the two groups. Based upon these data, it can be concluded that (1) FK506 pretreatment ameliorates the functional renal injury associated with I/R, (2) renal ischemia induces the release of TNF, and (3) FK506 pretreatment results in a significant inhibition of TNF production. These data suggest that the release of TNF may be responsible for the increasing of BUN and creatinine levels seen after renal I/R and that pretreatment of renal donors with FK506 may improve renal function in the immediate post-transplant period. © 1992 by Williams and Wilkins

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P<0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P<0.01) and thymidine kinase activity (P<0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P<0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation

FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion

Using a rat model, the effect of pre-treatment with FK 506 on hepatic ischemia/reperfusion injury was investigated. All control animals died within 72 h of the ischemia/reperfusion injury. Pre-treatment of the animals with FK 506 (0.3 mg/kg in 0.5 ml saline) administered intravenously improved survival. The most striking protection against fatal ischemia/reperfusion injury was achieved in rats that were given FK 506 6 and 24 h prior to the induction of the hepatic ischemic insult (70% and 80% 10-day survival rates, respectively). The hepatoprotective effect of FK 506 was assessed further in a second experiment in which the serum levels of tumor necrosis factor (TNF) and interleukin 6 (IL-6) were measured. These results suggest that a 60-min period of hepatic ischemia and subsequent reperfusion triggers the release of both TNF and IL-6, and that FK 506 pre-treatment (6 h before the ischemic episode) significantly inhibits the production and/or release of these two cytokines compared to untreated controls. These data provide additional information concerning the immunosuppressive and hepatoprotective activities of FK 506. Based upon these data, it is probable that FK 506 attenuates hepatic ischemia/reperfusion injury, at least in part, by reducing TNF and IL-6 levels. © 1993 Elsevier Scientific Publishers Ireland Ltd. All rights reserved

Modeling factors influencing the demand for emergency department services in ontario: a comparison of methods

<p>Abstract</p> <p>Background</p> <p>Emergency departments are medical treatment facilities, designed to provide episodic care to patients suffering from acute injuries and illnesses as well as patients who are experiencing sporadic flare-ups of underlying chronic medical conditions which require immediate attention. Supply and demand for emergency department services varies across geographic regions and time. Some persons do not rely on the service at all whereas; others use the service on repeated occasions. Issues regarding increased wait times for services and crowding illustrate the need to investigate which factors are associated with increased frequency of emergency department utilization. The evidence from this study can help inform policy makers on the appropriate mix of supply and demand targeted health care policies necessary to ensure that patients receive appropriate health care delivery in an efficient and cost-effective manner. The purpose of this report is to assess those factors resulting in increased demand for emergency department services in Ontario. We assess how utilization rates vary according to the severity of patient presentation in the emergency department. We are specifically interested in the impact that access to primary care physicians has on the demand for emergency department services. Additionally, we wish to investigate these trends using a series of novel regression models for count outcomes which have yet to be employed in the domain of emergency medical research.</p> <p>Methods</p> <p>Data regarding the frequency of emergency department visits for the respondents of Canadian Community Health Survey (CCHS) during our study interval (2003-2005) are obtained from the National Ambulatory Care Reporting System (NACRS). Patients' emergency department utilizations were linked with information from the Canadian Community Health Survey (CCHS) which provides individual level medical, socio-demographic, psychological and behavioral information for investigating predictors of increased emergency department utilization. Six different multiple regression models for count data were fitted to assess the influence of predictors on demand for emergency department services, including: Poisson, Negative Binomial, Zero-Inflated Poisson, Zero-Inflated Negative Binomial, Hurdle Poisson, and Hurdle Negative Binomial. Comparison of competing models was assessed by the Vuong test statistic.</p> <p>Results</p> <p>The CCHS cycle 2.1 respondents were a roughly equal mix of males (50.4%) and females (49.6%). The majority (86.2%) were young-middle aged adults between the ages of 20-64, living in predominantly urban environments (85.9%), with mid-high household incomes (92.2%) and well-educated, receiving at least a high-school diploma (84.1%). Many participants reported no chronic disease (51.9%), fell into a small number (0-5) of ambulatory diagnostic groups (62.3%), and perceived their health status as good/excellent (88.1%); however, were projected to have high Resource Utilization Band levels of health resource utilization (68.2%). These factors were largely stable for CCHS cycle 3.1 respondents. Factors influencing demand for emergency department services varied according to the severity of triage scores at initial presentation. For example, although a non-significant predictor of the odds of emergency department utilization in high severity cases, access to a primary care physician was a statistically significant predictor of the likelihood of emergency department utilization (OR: 0.69; 95% CI OR: 0.63-0.75) and the rate of emergency department utilization (RR: 0.57; 95% CI RR: 0.50-0.66) in low severity cases.</p> <p>Conclusion</p> <p>Using a theoretically appropriate hurdle negative binomial regression model this unique study illustrates that access to a primary care physician is an important predictor of both the odds and rate of emergency department utilization in Ontario. Restructuring primary care services, with aims of increasing access to undersupplied populations may result in decreased emergency department utilization rates by approximately 43% for low severity triage level cases.</p

Participant recruitment and retention in a pilot program to prevent weight gain in low-income overweight and obese mothers

<p>Abstract</p> <p>Background</p> <p>Recruitment and retention are key functions for programs promoting nutrition and other lifestyle behavioral changes in low-income populations. This paper describes strategies for recruitment and retention and presents predictors of early (two-month post intervention) and late (eight-month post intervention) dropout (non retention) and overall retention among young, low-income overweight and obese mothers participating in a community-based randomized pilot trial called <it>Mothers In Motion</it>.</p> <p>Methods</p> <p>Low-income overweight and obese African American and white mothers ages 18 to 34 were recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children in southern Michigan. Participants (n = 129) were randomly assigned to an intervention (n = 64) or control (n = 65) group according to a stratification procedure to equalize representation in two racial groups (African American and white) and three body mass index categories (25.0-29.9 kg/m², 30.0-34.9 kg/m², and 35.0-39.9 kg/m²). The 10-week theory-based culturally sensitive intervention focused on healthy eating, physical activity, and stress management messages that were delivered via an interactive DVD and reinforced by five peer-support group teleconferences. Forward stepwise multiple logistic regression was performed to examine whether dietary fat, fruit and vegetable intake behaviors, physical activity, perceived stress, positive and negative affect, depression, and race predicted dropout as data were collected two-month and eight-month after the active intervention phase.</p> <p>Results</p> <p>Trained personnel were successful in recruiting subjects. Increased level of depression was a predictor of early dropout (odds ratio = 1.04; 95% CI = 1.00, 1.08; p = 0.03). Greater stress predicted late dropout (odds ratio = 0.20; 95% CI = 0.00, 0.37; p = 0.01). Dietary fat, fruit, and vegetable intake behaviors, physical activity, positive and negative affect, and race were not associated with either early or late dropout. Less negative affect was a marginal predictor of participant retention (odds ratio = 0.57; 95% CI = 0.31, 1.03; p = 0.06).</p> <p>Conclusion</p> <p>Dropout rates in this study were higher for participants who reported higher levels of depression and stress.</p> <p>Trial registration</p> <p>Current Controlled Trials NCT00944060</p

High Pressure Effects on Superconductivity

The review is devoted to a discussion of the effects of high pressure imposed on superconducting materials. Low-temperature superconductors, high-temperature superconducting cuprates, and some unconventional superconducting compounds are investigated. Experimental as well as theoretical results regarding the pressure effects on Tc and other interesting properties are summarized.Comment: To be published in: "Frontiers in Superconducting Materials", Edt. A. Narlikar, Springer Verla

Angle-resolved photoemission spectroscopy of the cuprate superconductors

This paper reviews the most recent ARPES results on the cuprate superconductors and their insulating parent and sister compounds, with the purpose of providing an updated summary of the extensive literature in this field. The low energy excitations are discussed with emphasis on some of the most relevant issues, such as the Fermi surface and remnant Fermi surface, the superconducting gap, the pseudogap and d-wave-like dispersion, evidence of electronic inhomogeneity and nano-scale phase separation, the emergence of coherent quasiparticles through the superconducting transition, and many-body effects in the one-particle spectral function due to the interaction of the charge with magnetic and/or lattice degrees of freedom. The first part of the paper introduces photoemission spectroscopy in the context of strongly interacting systems, along with an update on the state-of-the-art instrumentation. The second part provides a brief overview of the scientific issues relevant to the investigation of the low energy electronic structure by ARPES. The rest of the paper is devoted to the review of experimental results from the cuprates and the discussion is organized along conceptual lines: normal-state electronic structure, interlayer interaction, superconducting gap, coherent superconducting peak, pseudogap, electron self energy and collective modes. Within each topic, ARPES data from the various copper oxides are presented.Comment: Reviews of Modern Physics, in press. A HIGH-QUALITY pdf file is available at http://www.physics.ubc.ca/~damascel/RMP_ARPES.pd

The role of diet in the aetiopathogenesis of inflammatory bowel disease

Crohn’s disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene–environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions