Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells

Background  

Dietary fatty acids may modulate inflammation in macrophages of the atherosclerotic plaque, affecting its stability. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) generally promotes inflammation, while the PUFAs of the n-3 series eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are considered anti-inflammatory. We determined how these PUFAs influence MMP-9 expression and secretion by the human monocytic cell line (MonoMac 6) at baseline and after 24-hour exposure. MMP-9 protein was measured by zymography and relative levels of MMP-9 mRNA were determined using quantitative real time PCR.     

Neuropeptide Y polymorphism significantly magnifies diabetes and cardiovascular disease risk in obesity: the Hoorn Study

The leucine7 to proline7 (Leu7Pro) polymorphism in preproneuropeptide Y (preproNPY) has been associated with accelerated atherosclerosis and type II diabetes, both of which are obesity-related diseases. The current study evaluated the impact of obesity on the disease risk linked to the Leu7Pro polymorphism of preproNPY in 393 elderly subjects. In 6 years follow-up, the polymorphism alone did not change the risk for abnormal glucose regulation, while obesity was associated with a significant 3-fold risk (odds ratio (OR) 2.95; 95% confidence interval (CI) 1.81-4.81, P<0.001) and the Leu7Pro polymorphism-obesity interaction, with a remarkable 12-fold risk (OR 12.33; 95% CI 1.18-128.35, P<0.05). The Leu7Pro polymorphism modified significantly the 10-year incidence of cardiovascular events, causing a 7.6-fold increase in the hazard ratio (HR 7.58; 95% CI 2.87-20.03, P<0.001) in the obese but not in the nonobese subjects. The results indicate that obesity may be a pivotal factor in multiplying the disease risk associated with the Leu7Pro polymorphism in preproNPY.     

p38alpha and p38delta mitogen-activated protein kinase isoforms regulate invasion and growth of head and neck squamous carcinoma cells

Recent studies indicate that the specificity of p38 mitogen-activated protein kinase (MAPK)-mediated cellular stress responses is determined by the expression pattern of the distinct p38 isoforms. Here, we have analysed the function of distinct p38 isoforms in the growth and invasion of head and neck squamous cell carcinomas (HNSCCs). Activation of p38 MAPK by arsenite resulted in inactivation of the ERK1,2 signaling pathway by dephosphorylation of MEK1,2 in primary human epidermal keratinocytes (HEKs), whereas in HNSCC cells this p38-mediated inhibition of the ERK1,2 pathway was absent. Quantitation of p38 pathway component mRNA expression in HNSCC cell lines (n=42) compared to HEKs (n=8) revealed that p38alpha and p38delta isoforms are predominantly expressed in both cell types and that MKK3 is the primary upstream activator expressed. Inhibition of endogenous p38alpha or p38delta activity by adenoviral delivery of corresponding dominant-negative p38 isoforms potently reduced MMP-13 and MMP-1 expressions, and suppressed the invasion of HNSCC cells through collagen. Dominant-negative p38alpha and p38delta inhibited squamous cell carcinoma (SCC) cell proliferation and inhibition of p38alpha activity also compromised survival of SCC cells. p38alpha and p38delta were predominantly expressed in HNSCCs (n=24) and nonneoplastic epithelium in vivo (n=6), with MKK3 being the primary upstream activator. Activation and expression of p38alpha and p38delta by tumor cells was detected in HNSCCs in vivo (n=16). Adenoviral expression of dominant-negative p38alpha or p38delta in cutaneous SCC cells potently inhibited their implantation in skin of severe combined immunodeficiency mice and growth of xenografts in vivo. Our results indicate that p38alpha and p38delta specifically promote the malignant phenotype of SCC cells by regulating cell survival, proliferation and invasion, suggesting these p38 MAPK isoforms as potential therapeutic targets in HNSCCs.     

Effect of Physical Activity Counseling on Disability in Older People: A 2‐Year Randomized Controlled Trial

OBJECTIVES: To study the effect of a physical activity counseling intervention on instrumental activity of daily living (IADL) disability. DESIGN: Primary care–based, single‐blind, randomized controlled trial. SETTING: City of Jyväskylä, central Finland. PARTICIPANTS: Six hundred thirty‐two people aged 75 to 81 who were able to walk 500 meters without assistance, were at most moderately physically active, had a Mini‐Mental State Examination score greater than 21, had no medical contraindications for physical activity, and gave informed consent for participation. INTERVENTION: A single individualized physical activity counseling session with supportive phone calls from a physiotherapist every 4 months for 2 years and annual lectures on physical activity. Control group received no intervention. MEASUREMENTS: The outcome was IADL disability defined as having difficulties in or inability to perform IADL tasks. Analyses were carried out according to baseline IADL disability, mobility limitation, and cognitive status. RESULTS: At the end of the follow‐up, IADL disability had increased in both groups (P<.001) and was lower in the intervention group, but the group‐by‐time interaction effect did not reach statistical significance. Subgroup analyses revealed that the intervention prevented incident disability in subjects without disability at baseline (risk ratio=0.68, 95% confidence interval=0.47–0.97) but had no effect on recovery from disability. CONCLUSION: The physical activity counseling intervention had no effect on older sedentary community‐dwelling persons with a wide range of IADL disability, although it prevented incident IADL disability. The results warrant further investigation to explore the benefits of a primary care–based physical activity counseling program on decreasing and postponing IADL disability.     

Overweight and Obesity in Old Age Are Not Associated with Greater Dementia Risk

OBJECTIVES: To describe the association between body mass index (BMI) and dementia risk in older persons. DESIGN: Prospective population‐based study, with 8 years of follow‐up. SETTING: The municipality of Lieto, Finland, 1990/91 and 1998/99. PARTICIPANTS: Six hundred five men and women without dementia aged 65 to 92 at baseline (mean age 70.8). MEASUREMENTS: Weight and height were measured at baseline and at the 8‐year follow‐up. Dementia was clinically assessed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: Eighty‐six persons were diagnosed with dementia. Cox regression analyses, adjusted for age, sex, education, cardiovascular diseases, smoking, and alcohol use, indicated that, for each unit increase in BMI score, the risk of dementia decreased 8% (hazard ratio (HR)=0.92, 95% confidence interval (CI)=0.87–0.97). This association remained significant when individuals who developed dementia early during the first 4 years of follow‐up were excluded from the analyses (HR=0.93, 95% CI=0.86–0.99). Women with high BMI scores had a lower dementia risk (HR=0.90, 95% CI=0.84–0.96). Men with high BMI scores also tended to have a lower dementia risk, although the association did not reach significance (HR=0.95, 95% CI=0.84–1.07). CONCLUSION: Older persons with higher BMI scores have less dementia risk than their counterparts with lower BMI scores. High BMI scores in late life should not necessarily be considered to be a risk factor for dementia.     

Correlation between Octopus perimetry and fluorescein angiography after strontium-90 plaque brachytherapy for subfoveal exudative age related macular degeneration

AIM—To evaluate the correlation between the central visual field and changes in fluorescein angiography and fundus photography in patients treated with strontium plaque radiotherapy for subfoveal exudative age related macular degeneration (AMD).METHODS—Octopus program 34 automated static perimetry, fluorescein angiography, and colour fundus photography were performed on 19 patients at baseline and at 12 months after strontium-90 plaque therapy. A schematic picture outlining the areas of hyperfluorescent neovascular membranes and subretinal blood was drawn of a projected 30° fundus fluorescein angiogram. This drawing was superimposed on the size adjusted Octopus visual field. The changes in retinal sensitivity were calculated and related to angiographic changes.RESULTS—Three of the 19 patients had a reliability factor (RF) >15% and were excluded from further analysis. In the remaining 16 patients the mean defect (MD) and loss variance (LV) values remained unchanged in patients showing regression of the choroidal neovascular membrane (CNVM) to irradiation at 12 months. MD was 7.7 (SD 1.7) at baseline and 7.6 (1.9) at 12 months (p = 0.86), and LV was 32.6 (13.9) at baseline and 32.4 (15.7) at 12 months (p = 0.94). However, in patients with progression of the CNVM at 12 months, both the MD and LV increased significantly during the 12 month follow up (MD from 7.3 (2.9) to 13.1 (3.6) ( p = 0.05) and LV from 31.0 (22.9) to 71.8 (24.1) (p = 0.017)). When comparing the mean retinal sensitivity in the area of the primary CNVM (including classic, occult, and haemorrhagic components), the results were analogous: in patients with a regression of the CNVM after irradiation the mean sensitivity remained almost unchanged. It was 10.3 (6.4) dB at baseline and 9.4 (7.3) dB at 12 months (p = 0.58). In five out of 11 patients (45%) with regression of the CNVM, the mean retinal sensitivity even improved by 2.0-5.0 dB in the area of the original lesion during follow up. Instead, in patients showing progression of the CNVM at 12 months, there was a significant loss in mean retinal sensitivity—from 9.9 (4.6) dB at baseline to 1.0 (1.1) dB at 12 months (p = 0.019). The mean retinal sensitivity in the area of the irradiated but clinically normal retina during follow up was not significantly altered (21.5 dB at baseline, 19.7 dB at 12 months (p = 0.10)).CONCLUSIONS—Regression of subfoveal choroidal membranes in AMD after focal strontium irradiation is connected with stabilisation or even improvement of retinal sensitivity in central visual field measured by automated perimetry. Strontium plaque irradiation does not change the sensitivity in clinically normal paramacular retina during a 12 month follow up.     

Aryl hydrocarbon hydroxylase activity in chemically induced and toremifene-treated mammary tumors in rats

Aryl hydrocarbon hydroxylase (AHH) and NADPH-cyto-chrome P450 reductase (NCR) activity of microsomes from liver, lungs, uterus and mammary tumors in dimethylbenz-antrachene-induced and torem'rfene-treated female Sprague-Dawley rats were studied. AHH and NCR activity in tumors and uteri was low compared with that in livers and lungs. The distribution of AHH in tumors was wide and skewed. It varied in different tumors of the same animal as widely as between different animals. The enzyme activity in tumors did not correlate with that in the liver, lungs or uterus of the same animal. Toremifene had no effect on AHH or NCR in tumor or liver, but it decreased them in lungs. Tumor AHH activity correlated with its overall growth rate and development stage. The results suggest that malignant transformation leading to the defect in growth regulation also confuses the complex regulatory system of AHH activity.     

Acute neurobehavioural toxicity of trichothecene T-2 toxin in the rat.

The acute effects of single oral doses, 0.4 and 2.0 mg/kg, of trichothecene T-2 mycotoxin on behaviour, motor performance and nociception were studied in male Wistar rats. Both doses are sublethal and did not cause overt acute signs of intoxication. In the open field test, 2.0 mg/kg of T-2 toxin increased motionlessness and decreased sniffing (P less than 0.05) 4 hr after the administration. The higher dose shortened step-through latencies in the test trial of the 24-hr passive avoidance test (two-way shuttle box). The exponential data analysis showed that, in those rats that did not learn to avoid the dark (unsafe) compartment of the box, the retention after 2.0 mg/kg of T-2 toxin was only 25% of that in controls (P less than 0.001). T-2 toxin had no effect on motor coordination in the rotarod test and in the bridge walking test 7-8 hr after administration. T-2 toxin had no effect on nociception in the hot place test 8.5 hr after administration. The results suggest that T-2 toxin has some inactivating effects on behaviour of rats, and it seems to cause an impairment in the passive avoidance test at dose 2.0 mg/kg.     

Respiratory effects of exposure to methacrylates among dental assistants

BACKGROUND: Case reports of occupational asthma in dental personnel have been published, but there is little data on the risk of respiratory disorders related to occupational exposure to methacrylates in dental assistants. The objective of this study was to investigate the relation of exposure to methacrylates to occurrence of respiratory symptoms and diseases among dental assistants. METHODS: A cross-sectional study of female dental assistants from the membership register of the Finnish Association of Dental Hygienists and Assistants was conducted in the Helsinki metropolitan area. A CATI was carried out to collect information on health and exposures. A total of 799 dental assistants participated (response rate 87%). RESULTS: Daily use of methacrylates was related to a significantly increased risk of adult-onset asthma (adjusted OR 2.65, 95% CI 1.14-7.24), nasal symptoms (1.37, 1.02-1.84), and work-related cough or phlegm (1.69, 1.08-2.71). Nasal symptoms showed a dose-response relation with increasing years of exposure to methacrylates, and those with >10 years of exposure had also increased risk of hoarseness, dyspnoea, and wheezing with dyspnoea. Dental assistants with a history of atopic diseases were particularly susceptible to exposure to methacrylates, the adjusted OR for adult asthma being in this group 4.18 (95% CI 1.02-28.55) and for nasal symptoms 2.11 (1.08-4.19). CONCLUSIONS: This study provides new evidence that the risk of adult-onset asthma, nasal symptoms and other respiratory symptoms increase significantly with daily use of methacrylates in dental assistants' work. The results suggest that exposure to methacrylates poses an important occupational hazard for dental assistants.     

A programme for developing nurses'' skills and nursing practice

In this paper we describe a programme for developing nursing care for patients with myocardial infarction (MI) and report some results of a study in which applicability and effectiveness of this programme were evaluated. To investigate how the programme influenced nursing practice, nurses' readiness (knowledge, skills, motivation, accountability) to provide care for MI patients was followed for 2 years. Data for the evaluation were collected by questionnaires from three categories of nurses, by analysing nursing documents before and 1 and 2 years after the programme started, and by keeping a continuous diary. This programme made an impact on many variables that measure changes in nursing practice and nurses' readiness to provide care. The implications of this programme for nursing practice, research, education and administration are discussed.