Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines

To investigate a possible link between bile acids and the pathogenesis of pancreatic cancer, we determined whether conjugated or unconjugated bile acids induced cyclooxygenase-2 (COX-2) in two human pancreatic cancer cell lines, BxPC-3 and SU 86.86. Bile acids are known promoters of gastric and colon cancer. We demonstrated previously that COX-2, an enzyme that catalyzes the synthesis of prostaglandins, is over-expressed in human pancreatic adenocarcinoma. Both human pancreatic cell lines were treated with conjugated and unconjugated bile acids. COX-2 mRNA and protein were determined. In addition, prostaglandin E2 (PGE2) synthesis was measured. Treatment with conjugated or unconjugated bile acids for 3 h up-regulated COX-2 mRNA. Chenodeoxycholate (CD) or deoxycholate at concentrations ranging from 12.5 to 100 micro M caused a dose-dependent induction of COX-2 protein with a maximal effect at 100 micro M. Induction of COX-2 protein by CD and deoxycholate was detected after treatment for 6 h with maximal induction at 12 h. Taurochenodeoxycholate, a conjugated bile acid, also caused dose-dependent induction of COX-2 but higher concentrations of bile acid (200-1200 micro M) were required. Levels of cyclooxygenase-1 were unaffected by bile acid treatment. Unconjugated and conjugated bile acids caused 7- and 4-fold increases in PGE2 production, respectively. Taken together, these findings suggest a possible role for bile acids in the pathogenesis of pancreatic cancer.     

Primary high-grade non-Hodgkin lymphoma of the trachea in an adolescent

Lymphomas belong to the most treatable and curable malignant tumors of childhood. They should always be considered among differential diagnosis, even in unusual locations, and tumor material should be processed adequately to reach true diagnosis. The authors report on a 16-year-old adolescent with a tracheal lymphoma, a rare location of lymphoma in childhood. Because only formalin-fixed tumor material was obtained, pathology showed two differential diagnoses and the entity could never be fully clarified as anaplastic plasmacytoma or plasmoblastic lymphoma. Thus, full lymphoma diagnostic workup should be performed even in tumors with atypical location.     

Zoning out crime and improving community health in Sarasota,Florida: "Crime Prevention Through Environmental Design"

Sarasota, Fla, used Crime Prevention Through Environmental Design (CPTED) principles to guide revitalization efforts in its crime-ridden North Trail area. A team of city planners, police officers, and architects examined land use and crime data and sought input from local businesses, residents, and community leaders. Beginning in 1990, interventions included increased police patrols to reduce prostitution and the creation of a new zoning district to encourage area redevelopment based on CPTED principles. Compared with the rest of Sarasota, from 1990 to 1998 the North Trail Corridor experienced decreases in calls for police service (P <.005), crimes against persons and property (P = not significant), and prostitution (P <.05). These results suggest that community design may be a useful tool for decreasing crime and improving community health.     

The impact of community design and land-use choices on public health: a scientific research agenda

The design of a community's built environment influences the physical and mental health of its residents. Because few studies have investigated this relationship, the Centers for Disease Control and Prevention hosted a workshop in May 2002 to help develop a scientific research agenda on these issues. Workshop participants' areas of expertise included physical activity, injury prevention, air pollution, water quality, urban planning, transportation, architecture, epidemiology, land use, mental health, social capital, housing, and social marketing. This report describes the 37 questions in the resulting research agenda. The next steps are to define priorities and obtain resources. The proposed research will help identify the best practices for designing new communities and revitalizing old ones in ways that promote physical and mental health.     

Improved survival in patients with type 1 diabetes mellitus after renal transplantation compared with hemodialysis: a case-control study

BACKGROUND: Diabetes mellitus is the leading cause of renal failure worldwide. The question of which treatment modality-hemodialysis versus renal transplantation-is associated with the lowest risk of cardiovascular morbidity and mortality in the diabetic end-stage renal disease (ESRD) population has not yet been investigated in a controlled trial. METHODS: We therefore conducted a case-control study of patients with ESRD caused by type 1 diabetes mellitus. The case patients were diabetics who received a renal graft between 1978 and 1997, whereas the controls were registered for renal transplantation but stayed on maintenance hemodialysis without ever undergoing transplantation. The groups were matched for age, sex, duration of diabetes, length of hemodialysis (up to the registration), and date of registration for renal transplantation. RESULTS: Kaplan-Meier life table analysis, based on 46 case patients and 46 controls, demonstrated a highly significant (P=0.0001) poorer survival in the control group compared with the case group. Logistic regression showed that hemodialysis was a significant risk factor for death (P=0.0002) and cardiovascular morbidity (P=0.0023). Patients with cardiovascular complications such as coronary artery and peripheral vascular events were significantly more frequent in the control group. Additionally tested risk factors for cardiovascular complications (serum cholesterol, arterial blood pressure, number of antihypertensive drugs, serum calcium, serum phosphate, and glucose control [hemoglobin A(1c)]) showed no significant correlation to survival or morbidity in either group by logistic regression. CONCLUSIONS: Renal transplantation is associated with a significantly improved survival compared with hemodialysis in patients with ESRD caused by type 1 diabetes mellitus. This seems to be a result of a reduced incidence of cardiovascular complications after renal transplantation.     

Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis

Intestinal carcinogenesis involves the successive accumulation of multiple genetic defects until cellular transformation to an invasive phenotype occurs. This process is modulated by many epigenetic factors. Unconjugated bile acids are tumor promoters whose presence in intestinal tissues is regulated by dietary factors. We studied the role of the unconjugated bile acid, chenodeoxycholate, in an animal model of familial adenomatous polyposis. Mice susceptible to intestinal tumors as a result of a germline mutation in Apc (Min/+ mice) were given a 10 week dietary treatment with 0.5% chenodeoxycholate. Following this, the mice were examined to determine tumor number, enterocyte proliferation, apoptosis and beta-catenin expression. Intestinal tissue prostaglandin E2 (PGE2) levels were also assessed. Administration of chenodeoxycholate in the diet increased duodenal tumor number in Min/+ mice. Promotion of duodenal tumor formation was accompanied by increased beta-catenin expression in duodenal cells, as well as increased PGE2 in duodenal tissue. These data suggest that unconjugated bile acids contribute to periampullary tumor formation in the setting of an Apc mutation.     

Peer Reviewed: Investment in Safe Routes to School Projects: Public Health Benefits for the Larger Community

Introduction

The Safe Routes to School (SRTS) program is designed to encourage active and safe transportation for children to school. This report examines the potential broader impact of these programs on communities within 0.5 mile (0.8 km) of schools.

Methods

We used a geographic information system to generate estimates of the land area within 0.5 mile of public schools in 4 U.S. Census-defined categories: 37 large urban areas, 428 small urban areas, 1088 metropolitan counties (counties in metropolitan statistical areas excluding the urban areas), and 2048 nonmetropolitan counties. We estimated population at the county level or at the U.S. Census-defined urban-area level using data from the 2000 U.S. Census.

Results

In large urban areas, 39.0% of the land area was within 0.5 mile of a public school, and in small urban areas, 26.5% of the land area was within 0.5 mile of a public school. An estimated 65.5 million people in urban areas could benefit from SRTS projects. In nonurban areas, 1% or less of land is within 0.5 mile of a public school.

Conclusion

Results suggest that SRTS projects in urban areas can improve the walking and bicycling environment for adults as well as for children, the target users. Investment in SRTS can contribute to increased physical activity among children and adults.     

p107 is a suppressor of retinoblastoma development in pRb-deficient mice

Hemizygosity for the retinoblastoma gene RB in man strongly predisposes to retinoblastoma. In the mouse, however, Rb hemizygosity leaves the retina normal, whereas in Rb^−/− chimeras pRb-deficient retinoblasts undergo apoptosis. To test whether concomitant inactivation of the Rb-related gene p107 is required to unleash the oncogenic potential of pRb deficiency in the mouse retina, we inactivated both Rb and p107 by homologous recombination in embryonic stem cells and generated chimeric mice. Retinoblastomas were found in five out of seven adult pRb/p107-deficient chimeras. The retinal tumors showed amacrine cell differentiation, and therefore originated from cells committed to the inner but not the outer nuclear layer. Retinal lesions were already observed at embryonic day 17.5. At this stage, the primitive nuclear layer exhibited severe dysplasia, including rosette-like arrangements, and apoptosis. These findings provide formal proof for the role of loss of Rb in retinoblastoma development in the mouse and the first in vivo evidence that p107 can exert a tumor suppressor function.