Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer.

Squamous cell carcinoma (SCC) of the tongue is the most common cancer in the oral cavity and has a high mortality rate. A total of 90 mobile tongue SCC samples were analysed for Bryne's malignancy scores, microvascular density, and thickness of the SCC sections. In addition, the staining pattern of cyclooxygenase-2, alphavbeta6 integrin, the laminin-5 gamma2-chain, and matrix metalloproteinases (MMPs) -2, -7, -8, -9, -20, and -28 were analysed. The expression of MMP-8 (collagenase-2) was positively associated with improved survival of the patients and the tendency was particularly prominent in females. No sufficient evidence for a correlation with the clinical outcome was found for any other immunohistological marker. To test the protective role of MMP-8 in tongue carcinogenesis, MMP-8 knockout mice were used. MMP-8 deficient female mice developed tongue SCCs at a significantly higher incidence than wild-type mice exposed to carcinogen 4-Nitroquinoline-N-oxide. Consistently, oestrogen-induced MMP-8 expression in cultured HSC-3 tongue carcinoma cells, and MMP-8 cleaved oestrogen receptor (ER) alpha and beta. According to these data, we propose that, contrary to the role of most proteases produced by human carcinomas, MMP-8 has a protective, probably oestrogen-related role in the growth of mobile tongue SCCs.

Measurement of oedema in irritant-exposed skin by a dielectric technique.

BACKGROUND: Easily applicable water-specific instruments measuring local oedema in skin are not available. The aim of this study is to demonstrate quantitative assessment of skin oedema with the dielectric technique by measuring increase of skin water content related to sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. METHODS: Irritant skin reaction and resulting oedema were induced by an irritant patch test on volar forearms in 12 healthy volunteers with the application of 1% SLS for 6 h. After occlusion the volunteers were divided into two groups: the patch test site of group I (six volunteers) received no treatment other than a base cream for the skin reaction, while for group II (six volunteers) a strong corticosteroid (clobetasol propionate) was applied on the irritant skin. During a follow-up of 72 h, erythema was scored visually, and irritant-induced oedema was measured with a novel water-specific instrument MoistureMeter-D. RESULTS: In the untreated irritant skin, a maximum increase of 45% in skin water content was found at 10 h postocclusion and water content was still elevated at 72 h. With these persons, the degree of oedema agreed well with the ultrasound-measured skin thickness (P=0.053). In the corticosteroid-treated skin, an increase of 8% in water content was measured during 72 h but there was no correlation between oedema and skin thickness. There was no correlation between erythema and oedema in untreated or corticosteroid-treated skin. CONCLUSION: The new instrument can easily be applied for noninvasive quantitative evaluation of local oedema and fluid retention in irritant-exposed skin.

Psychosocial work environment and indoor air problems: a questionnaire as a means of problem diagnosis.

AIMS: To examine the relation between the psychosocial work environment and the perceived indoor air problems measured by a questionnaire survey; and to discuss the role of a questionnaire as a means to enhance collaboration in the challenging multiprofessional process of solving indoor air problems. METHODS: The research material comprises surveys conducted in 1996-99 in 122 office workplaces with 11 154 employees. RESULTS: The association between the psychosocial work environment measured by the Indoor Air Questionnaire (MM-40) and the occupants' complaints concerning indoor air as well as symptoms attributed to indoor air was significant. Those who perceived their psychosocial work environment more negatively had more complaints regarding the indoor environment and more symptoms attributed to the indoor air. The association was detected among both genders, in every age group, among smokers and non-smokers, and respondents with an allergic or a non-allergic background. CONCLUSIONS: Results support the hypothesis that psychosocial factors in the work environment play a significant role in indoor air problems at workplaces. The survey data can be used as a reference database for future studies, and in occupational health care practice when the working conditions of individual workplaces are estimated. The MM-40 could be useful as a practical screening method in field work for analysing the role of the psychosocial work environment among the different background factors of an indoor air problem. However, in order to interpret and evaluate the significance of the results concerning a single workplace, more information on the organisation is needed, as well as cooperation and discussions with the staff. Further studies of the reliability and validity of the psychosocial questions in MM-40 are also needed.

Nitric oxide and inflammatory response in simulated extracorporeal circulation.

BACKGROUND: Simulated extracorporeal circulation (SECC) induces inflammatory reaction. Nitric oxide (NO) has pro-and anti-inflammatory properties. NO role in SECC-related inflammatory response is unclear. The aim of this study was to clarify if NO affects the foreign-surface induced leukocyte activation during SECC. METHODS: Human blood was circulated through SECC during 3 hours. Control group C was ventilated with oxygen/air mixture and the study group with oxygen/air mixture and NO. Leukocyte activation was measured as serum levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), lactoferrin (LF), interleukin-1-beta (IL-1 beta) and interleukin-10 (IL-10). Oxygen free radical production capacity was evaluated with chemiluminescence. NO metabolites nitrite/nitrate were estimated in serum. RESULTS: Leukocyte granule release increased over time. Addition of NO significantly increased MPO, HNL and LF release. The average difference increased with SECC duration. NO addition did not significantly affect measured interleukins concentration or oxygen free radical production capacity. NO metabolites increased significantly in the NO circuits. CONCLUSIONS: Results indicate that NO addition during SECC is pro-inflammatory and has no effect on oxygen free radical production and interleukin release.

Discrepant outcome between myocardial energy-related metabolites and infarct size limitation during retroperfusion of the coronary sinus.

The basic idea of retroperfusion of the coronary sinus (RCS) is to ameliorate detrimental consequences of myocardial ischaemia. Several experimental models of RCS have been introduced, most with an emphasis on functional myocardial status. Since only few studies have been devoted to energy metabolic considerations and none to continuous monitoring of energy-related metabolites of myocardium during RCS, we here present such a study using microdialysis. This study comprised the following components: Coronary occlusion and drainage on the beating heart with RCS-assist (60 min), hypothermic (30 degrees C) extracorporeal circulation (ECC) and cardioplegia (45 min), reperfusion and rewarming to 38 degrees C on ECC (30 min). The microdialysis analytical outcome mainly reflected anaerobic energy metabolism in potentially ischaemic myocardium. Additionally, a pronounced increase of microdialysate content of lactate, pyruvate and guanosine was observed in non-ischaemic myocardium especially during the reperfusion phase. The planimetric calculation revealed an infarct size reduction from 69% to 19% and was not correlated to clear-cut improvements of potentially ischaemic myocardial energy metabolism. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival.

Inflammatory response during simulated extracorporeal circulation with addition of nitric oxide.

BACKGROUND: Heart operations performed with extracorporeal circulation (ECC) are associated with an inflammatory response. This response is partially due to granulocyte activation. Leukocyte derived free radicals are involved in tissue injury. The purpose of this study was to observe whether nitric oxide influence the inflammatory response during simulated ECC. METHODS: In a model of simulated extracorporeal circulation, fresh whole human blood mixed with Ringer's solution was circulated through a heart-lung machine for three hours. In five circuits NO was added to oxygen/air mixture (group N), while five other circuits were ventilated with oxygen/air mixture (group C). The methods for estimating the inflammatory response were determination of oxygen free radicals production capacity, using chemiluminescence, and measurements of concentration of granulocyte derived proteins (myeloperoxidase and human neutrophil lipocalin). RESULTS: All measured parameters were similarly independent of additional supply of nitric oxide almost throughout extracorporeal circulation time. The sole significant difference between the two groups was found at an early stage of extracorporeal circulation, when luminol-enhanced chemiluminescence in whole blood was higher in the N group (1,500, 1,470-1,950 vs 1,038, 750-1,050 in the control group; medians with quartiles). A similar tendency was observed in lucigenin-enhanced chemiluminescence at 60 min of extracorporeal circulation (625, 560-875 in the N group vs 400, 360-525 in the control group; medians with quartiles). CONCLUSIONS: Nitric oxide supply does not influence inflammatory response during three hours long extracorporeal circulation, although some protective effect on hydrogen peroxide production in whole blood was detected in the initial phase of extracorporeal circulation.

Nitric oxide increases leukocyte granule release during simulated extracorporeal circulation.

BACKGROUND: Nitric Oxide (NO) is reported to possess anti-inflammatory properties. The aim of this study was to investigate if nitric oxide affects leukocyte response during simulated extracorporeal circulation (SECC). METHODS: Human blood was circulated for 23 hours through SECC circuit. Control group C (n = 5) was ventilated with an oxygen/air mixture, and NO was added in the study group (n = 5). Leukocyte response was determined by release of myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) and by oxygen free radical production, estimated using chemiluminescence. RESULTS: Addition of NO significantly increased MPO at 30 minutes and 120 minutes of SECC and HNL at 120 minutes of SECC. Oxygen free radical production in whole blood was generally not affected by NO. Similarly, no significant differences were observed between the groups with regard to the chemiluminescence in isolated granulocytes. CONCLUSIONS: Nitric oxide increased release of leukocyte granule derived proteins; MPO and HNL at an early stage of simulated extracorporeal circulation. At the same time, nitric oxide did not affect the whole blood and leukocyte capacity to produce oxygen free radicals.