Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma and levels of prostaglandin E2 and 15-deoxy-delta12,14-prostaglandin J2 in human breast cancer and metastasis

Cyclooxygenase-2 (COX-2) expression and peroxisome proliferator-activated receptor-gamma (PPARgamma) inactivation are linked to increased risk of human breast cancer. The purpose of our study was to examine the relationship between COX-2 (with the resulting prostaglandins E(2), PGE(2)) and PPARgamma (and its natural endogenous ligand 15-Deoxy-Delta(12,14)-prostaglandin J(2), 15d-PGJ(2)) at various stages during the development of human breast cancer and its progression to metastasis. Human breast tissue specimens were collected from normal breasts or from individuals with fibrocystic disease and served as controls (n = 22). Tissues were also collected from uninvolved (n = 25), tumor (n = 25) and lymph node metastasis (n = 15) regions from breast cancer patients. COX-2 and PPARgamma mRNA expression were increased and downregulated, respectively, in tissues from cancer patients compared to controls. Metastatic tissues tended to have higher alterations compared to non-metastatic tissues (p < 0.05). These altered expressions in COX-2 and PPARgamma were paralleled by increases in the tissue levels of PGE(2) and decreases in 15d-PGJ(2). A significant inverse correlation was found between PGE(2) and 15-d-PGJ(2) (r = -0.51, p < 0.05). Significant correlations (p < 0.05) were also obtained between COX-2 and PPARgamma mRNA (inverse, r = -0.72) and between COX-2 and PGE(2) (direct, r = 0.68). Increases in COX-2 mRNA expression and levels of PGE(2) and down-regulation of PPARgamma mRNA expression and 15d-PGJ(2) levels were characterized as predictors of breast cancer risk (p < 0.05). Our results suggest that the altered expression of COX-2 and PPARgamma and the subsequent modulation in the tissue levels of PGE(2) and 15-d-PGJ(2) may influence the development of human breast cancer and its progression to metastasis.     

Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats

BACKGROUND: The binding of 5-lipoxygenase (5-LO) to the 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes (LT) from arachidonic acid. We have shown that FLAP antagonist administration decreased proteinuria in glomerulonephritic patients. In this follow-up study, we assessed the role for FLAP in a rat model of streptozotocin-induced diabetic nephropathy. METHODS: Diabetic rats were treated for 4 weeks with FLAP (BAY X-1005, 200 mg/kg) or 5-LO (Zileuton, 80 mg/Kg) antagonists. Proteinuria, renal function and LT production was assessed. We also determined protein permeability of cultured glomerular endothelial cells (which possess no 5-LO) by measuring their permeability to radiolabeled albumin with and without FLAP antagonists. RESULTS: FLAP mRNA levels increased dramatically in glomeruli from diabetic animals compared to controls. Inhibition of FLAP (but not inhibition of 5-LO) reduced proteinuria, with no effect on estimated glomerular filtration rate. Interestingly, diabetes-induced rises in urinary excretion and glomerular production of leukotrienes were not modified by the inhibitors. Increased FLAP expression in glomerular endothelial cells in culture was associated with an increase in albumin permeability, and this increase was abolished by FLAP antagonists. On the other hand, addition of LTA(4) led to increases in leukotriene formation and in permeability. This increase in permeability was also reduced by co-incubation with FLAP antagonists, whereas the increase in leukotriene synthesis was not modified. CONCLUSIONS: These results suggest a role for FLAP other than the activation of 5-LO, possibly in protein handling, and point to FLAP antagonists as anti-proteinuric agents.     

Environmental awareness and worry among high school teachers in Kuwait

Industrialization has provided humanity with many material and social benefits. Unfortunately, it has also brought about many material and social problems, one of which is environmental pollution that nowadays poses a major threat not only to humans, but also to all life on earth. The aim of the present study is to assess the level of environmental awareness among high school teachers in Kuwait; to study the extent of their environmental worry; and to evaluate the relationship between their environmental awareness and worry, and how they vary with different socio-demographic variables. A cross sectional study of 461 high school teachers was conducted using a random multistage cluster sample design. The target population comprised public high school teachers (males and females) in 2 governorates, Hawalli and Ahmadi. Data collection was performed using a structured anonymous self-administered questionnaire covering the environmental awareness and environmental worry checklists. The sample involved 499 teachers. About 60% of the teachers had high level of environmental awareness and almost half of them had high level of environmental worry. Both scores increased with increasing age, years of experience, level of education of the spouse, presence of children and being non-Kuwaiti. Males scored higher in both scores, but the difference was only significant in the part concerning environmental worry. The level of teachers' environmental worry was significantly positively related to their environmental awareness.     

The imaging appearances of hydatid disease at some unusual sites

On reviewing our cases of hydatid disease seen over a period of 20 years (1978-1998), we encountered a number of unusual radiological appearances and sites, which are demonstrated in this pictorial review. We briefly discuss the pathology of hydatid disease and its complications.     

Factors influencing health promoting activities of mothers caring for ventilator-assisted children

The extensive care a ventilator-assisted child (VAC) requires when cared for in the home can impact the mother's ability to participate in health promotion activities. The purpose of this study was to examine health promotion activities and the relationships among functional status of the child, impact of the illness on the family, coping, social support, and health promotion activities of mothers who care for ventilator-assisted children at home. Thirty-eight primary female caregivers, mostly mothers, participated in the study and completed the Personal Lifestyle Questionnaire (PLQ), measures of child's functional status, impact of the illness on the family, coping, social support, and demographic data. Findings revealed that the mothers scored low on the nutrition, exercise, relaxation, and general health promotion subscales of the PLQ. Functional status of the child and coping were positively correlated with participation in health promotion activities, whereas impact of the child's illness on the family was inversely related to health promotion of the mothers. Regression analysis revealed that functional status of the child and coping were significant predictors of mothers' participation in health promotion activities. The high demands associated with caring for a VAC with poor functioning can be a significant risk factor for not participating in health promotion activities. Nurses need to help mothers with coping and finding resources to help mediate the stress related to caring for their child, thereby helping the mothers to maintain their own health.     

Human melanoma cells release soluble and functional receptors

Cytokines play important roles in the growth and growth arrest of cancer cells. IL-13 via an IL-4R alpha/IL-13R alpha 1 heterocomplex receptor inhibits the growth of renal cell carcinoma cells (RCC). However, it does not inhibit the growth of glioblastoma cells that express the IL-13R alpha 2 chain. In the present studies we investigated whether melanoma cells express IL-13R alpha 1 and IL-13R alpha 2 chains as well as whether they respond to IL-13. Membrane IL13R alpha 2 was co-expressed with IL-4R alpha and IL-13R alpha 1 chains in three of six tested melanoma cell lines. Furthermore, the IL-13R alpha 2 positive cell lines, release a soluble form of IL-13R alpha 2, specifically under IL-13 but not IL-4 stimulation. The release of soluble IL-13R alpha 2 was inhibited by various metalloproteinase inhibitors and EDTA inhibits the biological response to IL-13.     

Assessment of synovitis in early rheumatoid arthritis by CXCL13 serum levels and power Doppler ultrasonography: Correlation with disease activity

Aim of the workAssessment of synovitis in rheumatoid arthritis (RA) is a major issue for proper treatment; it has been proven that high resolution ultrasound (US) examination could be of valuable help. The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. We aimed to find out the presence of synovitis in patients with recent-onset RA and its correlation with disease activity.Patients and methodsWe evaluated 30 patients with early RA for the presence and degree of synovitis by performing high resolution US and obtaining serum CXCL13 levels. In addition, we correlated these results with disease activity score 28 (DAS 28). Results of high resolution US and serum CXCL13 were also obtained for 20 healthy age- and sex-matched volunteers and served as controls.ResultsSerum CXCL13 level was significantly increased in early RA patients vs. controls (p < 0.001). High resolution US revealed that RA patients had a significant increased synovial thickness and high power Doppler US score. In RA patients, DAS 28 had a significant correlation with serum CXCL13 (r = 0.42, p = 0.02), synovial thickness (r = 0.39, p = 0.03) and power Doppler US score (r = 0.43, p = 0.02). Serum CXCL13 level correlated with synovial thickness (r = 0.63, p = 0.001) and power Doppler US score (r = 0.69, p = 0.001).ConclusionRecent-onset RA patients suffer from synovitis as evidenced by significantly increased serum CXCL13 and by high resolution US. Serum CXCL13 is a reliable marker of synovial inflammation which correlates better with synovial thickening and power Doppler US scores than DAS28.