Assessing the performance of environmental management in academic research laboratories.

Managing environmental risk is essential to ensure organisations minimise their impact on the environment, comply with environmental legislation and maintain their reputation in an increasingly environmentally aware society. Organisations frequently use management systems to plan and execute routine environmental assessments, however environmental impacts may still arise from routine activities or accidents that could be avoided by effective environmental management. Currently there is no method for an organisation to assess the level of awareness their employees have of activities that may lead to an environmental impact, or the level of uptake of environmental management processes. Therefore, the Environmental Management Performance Assessment (EMPA) process was developed to enable organisations to self-assess existing environmental management processes by survey of their employees. The EMPA process was aligned to key phases of the Deming Cycle and involves development and distribution of a survey to organisation employees. The responses are then used to recognise areas for improvement by progression through a bespoke flow chart integrated with the initial survey. This enables demonstration of how particular hazards arise from insufficient awareness at different stages in the Deming Cycle and how these hazards can have wider, reputational, economic, and legislative consequences. The process was trialled by surveying academic researchers on the environmental management processes in their laboratories as a sample set.

Are insulin resistance and non-alcoholic fatty liver disease associated with Peyronie's disease? A pilot study.

Risk factors for Peyronie's disease (PD) are serum lipid abnormalities, hypertension and type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation are key-players in the pathogenesis of arterial diseases, leading to insulin resistance (IR), which is a major determinant of non-alcoholic fatty liver disease (NAFLD). We studied the potential relationship between PD, IR, and NAFLD. Forty-nine male patients were enrolled, fulfilling the well-accepted diagnostic criteria of stable PD. Fifty male individuals without PD, well-matched for age and BMI, were selected as the control group. Comorbidities (T2DM and hypertension), as well as the lipid profile and the glucometabolic asset, were evaluated. The triglycerides/HDL ratio (TG/HDL-C ratio) with a cut-off of ≥3 and the triglycerides-glucose index (TyG) with an optimal cut-point of 8.5 were used for diagnosis of IR and NAFLD, respectively. NAFLD diagnosis was confirmed by the presence of bright liver at ultrasonography. Hypertension was found more frequently in PD patients than in no-PD subjects (P=0.017), independently of age (P=0.99). Both IR and NAFLD were significantly associated with the presence of PD in our population of men (P=0.043 and 0.0001, respectively), no matter how old (P=0.11 and 0.74, respectively). At logistic regression, NAFLD was the only predictor of the PD presence (p=0.021). The AUROC of TyG to predict PD was 0.7437 (sensitivity 67.35% and specificity 80%) with a percentage of correctly classified patients of 73.74%. Oxidative stress markers were significantly associated with NAFLD. Testosterone level was significantly low in the subjects with NAFLD in cross-sectional analyses. Both factors, i.e., oxidative stress and hypogonadism, are central to PD pathogenesis. In conclusion, NAFLD and IR are strongly associated with PD. The pathogenic link between these conditions and the underlying mechanisms are only hypothetical and thoroughly summarized in the discussion.

Natural orifices transluminal endoscopic surgery (NOTES): an overview of technical challenges and complications of transgastric procedures in anesthetized pigs.

AIM: Natural orifice transluminal endoscopic surgery (NOTES) is a new reality that is progressively gaining popularity in the scientific community. The aim of this study was to report the authors' experience with various peroral transgastric procedures performed on the porcine model. The technical difficulties and challenges that arose were also analyzed. METHODS: Ten anesthetized pigs, divided into an acute (3) and a survival group (7) underwent the following procedures using a double channel endoscope: peritoneoscopy (10), cholecystectomy (6),splenectomy (3), and gastrojejunostomy (3). RESULTS: All the procedures were completed successfully. There was one complication related to the gastric wall incision. In the survival experiment group all pigs (4) submitted to biliare procedures made an uncomplicated recovery after a follow-up period of 2 weeks. Gastrojejunostomies (3) were instead graved by one technical failure (anastomosis disruption at post-mortem examination) and one case of mortality (premature euthanasia for evidences of sepsis). Complete gastric cleansing was impossible to achieve and overinflation was a common problem. The creation of gastro-enteric anastomoses was technically difficult with the current available devices. CONCLUSION: Transgastric endoscopic surgery is technically feasible in a porcine model. A new instrumentation is needed and could strongly help to overcome the technical difficulties highlighted. More extensive animal studies are mandatory in order to evaluate the benefits and the limitations of this new technique.

Carotid endarterectomy under local anesthesia in elderly: is it worthwhile?

Carotid endarterectomy (CEA) has a positive effect on stroke free survival in patients with either symptomatic or asymptomatic severe carotid bifurcation stenosis. However, most trials have excluded elder patients. In addition, concerns have arisen regarding the benefits of CEA in the elderly population, especially in women. In this study, we performed an outcome analysis in patients undergoing CEA comparing those eighty and older to their younger counterparts. A total of 262 carotid operations were performed under local anaesthesia between 1998 and 2004; 76 (34%) were carotid reconstructions in 70 patients over 75 yr of age. Twenty patients (26%) presented with asymptomatic critical stenosis. Transient ischemic symptoms were the reason for presentation in 35 patients (46%). Progressive stroke was documented in two patients (3%) and a stroke with persisting neurological deficit was demonstrated in 19 cases (25%). Coronary artery disease was present in 47 patients (38%) and arterial hypertension in 55 (72%). Fifty-nine patients (84%) were classified as ASA group 3. Seventy-one thromboendarterectomies of the carotid bifurcation with direct closure were performed. Five patients had other types of reconstruction. Postoperative complications occurred in three patients. One had a transient neurological deficit and another a lethal stroke; the third patient died from myocardial infarction. The in-hospital mortality was 2.9%, which was not significantly higher than the results of the reconstructions in younger patients (1.5%). Surgery for carotid artery occlusive disease under local anaesthesia can be safely performed in selected patients of more than 75 yr of age.

Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.

A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.

Replacement of aromatic or heteroaromatic groups in nonsteroidal antiinflammatory agents with the ferrocene group.

Ferrocene analogues of the antiinflammatory agents tolmetin (1), fenbufen (2), flurbiprofen (3), and fenclofenac (4) were synthesized and tested for biological activity. The derivatives exhibited little or no antiarthritic or platelet antiaggregatory activity, indicating that the ferrocene moiety is a poor bioisostere for aromatic or heteroaromatic groups in nonsteroidal antiinflammatory agents.

Benzothiazole hydroxy ureas as inhibitors of 5-lipoxygenase: use of the hydroxyurea moiety as a replacement for hydroxamic acid.

A novel series of N-[(2-benzothiazolylthio)alkyl]-N'-hydroxyurea derivatives (9-25) was synthesized and evaluated for biological activity as inhibitors of 5-lipoxygenase both in vivo (mouse zymosan peritonitis assay) and in vitro (Ca2+ ionophore-stimulated human peripheral blood leukocyte model). The compounds of this series were based on the corresponding hydroxamic acid derivatives (1, 3, 4, and 5) which were moderately active in vitro but inactive in vivo. A number of compounds in the hydroxyurea series exhibited oral activity for 5-lipoxygenase inhibition. Results of studies relating structure to in vivo and in vitro 5-lipoxygenase activity are reported.

[Endoscopic palliative treatment of the common bile duct at the hepatic hilum. Results in 583 patients treated in a single center over a 10-year period]. / Trattamento palliativo per via endoscopica delle stenosi della via biliare principale all'ilo epatico. Risultati in 583 pazienti trattati in un singolo Centro in 10 anni.

BACKGROUND: The outcomes of endoscopic biliary drainage for malignant stenoses at the hepatic hilum were retrospectively evaluated. METHODS: From January 1990 to June 2001, 583 patients, 368 males, average age 69+/-18.5 years, were recruited. Endoscopic procedure consisted of insertion of 1 ore multiple stents, plastic or metallic, across the stricture, under mild sedation. RESULTS: Successful stent insertion was achieved in 518/583 (88.8%) patients and successful drainage in 474 (81.3%) patients. Early complications were observed in 101 (17.3%) patients with related-mortality of 17 (2.9%) patients. Late complications occurred in 39.9% of patients. Survival was of 189 days, on average. CONCLUSIONS: Endoscopic palliation should be the initial management of choice for malignant biliary stenoses at the hepatic hilum.

[Ultrasound-guided endoscopic drainage, without radiological examination, in patients with neoplastic biliary obstruction. Preliminary results]. / Sulla possibilità di drenaggio endoscopico, sotto guida ecografica, senza controllo radiologico, in pazienti con stenosi neoplastiche della via biliare principale. Risultati preliminari.

AIM: Endoscopic stent insertion has become the preferred method for palliation of malignant biliary obstruction. Currently, endoscopic stent placement involves the use of contrast media and radiological equipment to achieve direct opacification of the biliary duct systems, and to determine the location and the extension of biliary obstruction. This report proposes a new combination of ultrasonography and biliary endoscopy, with endoscopic stent placement entirely performed under US-guidance. METHODS: US-guided stent placement was carried out in 8 patients. A guide-wire and a guiding-catheter were endoscopically introduced and identified, by US, the common bile duct across the stricture. Hydromer-coated polyurethane angled stents (10F) were finally inserted over the guide-wire/guiding-catheter by a pusher tube system. RESULTS: Successful stent insertion was achieved in all patients. There were no complications. Successful drainage, with substantial reduction in bilirubin level, was achieved in all patients (14.2+/-9.5 vs 4.2+/-2.9 mg/dl at 1 week). CONCLUSION: Endoscopic stent placement performed under US-guidance, is safe and effective. Further studies in a larger series, including more proximal strictures are suggested.

Nonlocal properties of dynamical three-body Casimir-Polder forces.

We consider the three-body Casimir-Polder interaction between three atoms during their dynamical self-dressing. We show that the time-dependent three-body Casimir-Polder interaction energy displays nonlocal features related to quantum properties of the electromagnetic field and to the nonlocality of spatial field correlations. We discuss the measurability of this intriguing phenomenon and its relation with the usual concept of stationary three-body forces.

Potentiation of Balb/3T3 fibroblast proliferative response by interleukin-1 and epidermal growth factor.

Balb/3T3 fibroblasts respond to interleukin-1 (IL-1) by proliferating in a dose-dependent fashion. Increasing proliferative responses were observed with increasing IL-1 concentration in serum-free medium when the medium was supplemented with insulin, transferrin, and selenium. This response was evident only if the cell culture medium also contained the cyclooxygenase inhibitor indomethacin. When another fibroblast mitogen, epidermal growth factor (EGF) was cocultured with either purified monocyte-derived IL-1 beta or recombinant IL-1 beta, there was a potentiation of proliferation above the expected additive response. Unexpectedly, the response to recombinant IL-1 alpha was only additive with EGF. This suggests that IL-1-mediated activation of synovial fibroblasts in rheumatoid arthritis may be compounded by EGF as well as by other fibroblast mitogens secreted by cells found in the joint. The results further suggest that IL-1 and EGF interactions may play a significant role in wound healing, scarring, and bone resorption. In addition, these results imply that there may be different cellular activation pathways brought to bear in vivo which may depend, in part, on the IL-1 isotype available.

Substance P, neurokinin A, and neurokinin B induce generation of IL-1-like activity in P388D1 cells. Possible relevance to arthritic disease.

Near nanomolar concentrations of substance P induce production of IL-1 or an IL-1-like activity in the mouse macrophage cell line P388D1. Moreover, this could be accomplished with the carboxyl-terminal octapeptide substance P4-11, and could be inhibited with the substance P antagonist [D-Pro2, D-Trp7,9]-substance P. Two other mammalian neurokinins, neurokinin A and neurokinin B, were also found to induce secretion of IL-1-like activity in P388D1 cells. These findings suggest that activation of immune cells by neuromodulators can contribute to the maintenance of the chronic inflammatory state and the immunopathology observed in arthritic disease mediated by IL-1. The results also suggest that one approach to the treatment of rheumatoid arthritis might be to attempt to inhibit the local effects of immuno-modulatory neuropeptides, specifically the neurokinins, in affected joints.

A new assay for the measurement of mediator release from rat peritoneal mast cells.

In this report, we describe a new in vitro experimental system for monitoring the release, and inhibition of release, of [3H]-serotonin from rat peritoneal mast cells, which can be used as a novel screen for evaluation of compounds effective in immediate hypersensitivity reactions. This assay is an improvement on existing assays since the cells are not required to be exposed to hormones at any time during the procedure. In this assay, 1 microgram/ml of compound 48/80 consistently produced a 6- to 8-fold-increase in release of serotonin with a low background release of 4-5%. Disodium chromoglycate (DSCG), a standard inhibitor of histamine release, effectively inhibited compound-48/80-stimulated serotonin release with an average I50 of 2.1 X 10(-4) M. Several other potential antiasthmatic agents were far more potent than DSCG.

Antagonism by ETYA of the effects of leukotrienes on ileum and lung parenchymal strips independent of effects on arachidonic acid metabolism.

5,8,11,14-Eicosatetraynoic acid (ETYA), a compound which inhibits both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism, antagonized the contraction of segments of guinea-pig ileal longitudinal muscle produced by SRS-A (IC50 = 2.73 microM). This activity was unaffected by pretreatment of the tissues with 10 microM indomethacin. Phenidone, another mixed cyclooxygenase-lipoxygenase inhibitor, was inactive. FPL-55712, an SRS-A antagonist, was a very potent inhibitor (IC50 = 0.011 microM). BW755C and NDGA nonselectively inhibited the contractions of the guinea-pig ileal longitudinal muscle induced by SRS-A or histamine. ETYA antagonized the contraction of the guinea-pig ileal strip produced by 6 nM synthetic LTC4 (IC50 = 9.3 microM). FPL-55712 demonstrated an IC50 of 0.3 microM in a similar series of experiments. ETYA, 1, 3 or 10 microM did not inhibit the contractions elicited by 0.5 microM of histamine. This was not a tissue-selective effect since 100 microM ETYA antagonized the LTC4-induced contraction of the guinea-pig lung parenchymal strip preparation. These data demonstrate that ETYA antagonized the contractile effect of the leukotrienes on tissues from the gastrointestinal tract and lung. Furthermore, the inability of indomethacin or phenidone to inhibit the contractile response suggests that antagonism by ETYA may occur by a mechanism independent of cyclooxygenase and lipoxygenase enzymes.

Enhancement of in vitro lipopolysaccharide-stimulated interleukin-1 production by levamisole.

The production of interleukin-1 (IL-1) by the P388D1 mouse macrophage cell line and by adherent peritoneal exudate cells (PMs) was examined. In vitro IL-1 production by P388D1 cells treated with lipopolysaccharide (LPS) was enhanced by coculture with levamisole (0.1 to 10 microM). Oral administration of levamisole (3 mg/kg) to mice also resulted in potentiation of in vitro IL-1 production by thioglycollate-elicited peritoneal macrophages in response to in vitro LPS stimulation. Potentiation was approximately twofold. IL-1 production in the absence of LPS by either the P388D1 cells or the PMs was nil, and levamisole did not directly stimulate IL-1 production in these cases. IL-1 activity in the culture supernatants was measured by thymocyte comitogenic assays. The immunochemical identify of the thymocyte comitogenic activity as IL-1 alpha was confirmed by neutralization with a specific goat anti-mouse IL-1 alpha antiserum. These results suggest that one mechanism by which levamisole acts to normalize and restore immune responses may be enhancing the signals which enable activated macrophages to secrete IL-1.