An investigation of reliability and validity of the LS/CMI with French offenders.

INTRODUCTION: The Level of Service/Case Management Inventory (LS/CMI) is one of the best-known recidivism risk instruments. In France, this scale is rarely used because no study had yet been carried out to confirm its psychometric properties on samples of French offenders. The aim of this study was to test the psychometric properties of the LS/CMI on samples of violent French prisoners. METHOD: The Level of Service/Case Management Inventory, the BARR-2002R, Historical Clinic Risk-Scale 20 and the Risk for Sexual Violence Protocol were administered to 128 violent offenders. RESULTS-DISCUSSION: The results showed good internal consistency, reliability and convergent validity of the LS/CMI. Assault, robbery and sexual assault were correlated with the LS/CMI. All of these results are discussed and analysed using the international reference literature. CONCLUSION: Confirmation of the psychometric properties of the LS/CMI among French offenders to allow it to be used to assess the risk of recidivism of offenders.

Effectiveness of Selected Air Cleaning Devices During Dental Procedures.

INTRODUCTION: The recent COVID-19 pandemic has underscored the necessity of protecting health care providers (HCPs) against the transmission of infectious agents during dental procedures. To this end, the effectiveness of several air cleaning devices (ACDs) in reducing HCPs exposure to aerosols generated during dental procedures was estimated, separately or in combination with each other. These ACDs were a chairside unit capturing aerosols at the source of generation, and four ambient ACDs: a portable ambient ACD; a negative pressure module; a custom made, fan-operated and wall-mounted air filter (WMAF); and a smaller and passive version of the latter. The last three ACDs were intended for mobile dental clinics (MDCs) only. MATERIALS AND METHODS: This assessment was performed in two different environments: in a dental clinic operatory and in a MDC. Two dental personnel, acting in the roles of dentist and dental assistant, performed on simulated patient aerosol-generating and non-aerosol-generating procedures. For each 5-minute scenario, the cumulative exposure to airborne particulate matter 10 µm in size or smaller (PM10) was determined by calculating the sum of all 1 second readings obtained with personal and ambient air monitors. The effectiveness of the ACDs in capturing PM10 was estimated based on the capability of the ACDs to keep PM10 level at or below the initial background level. RESULTS: In all conditions assessed in the dental clinic operatory, when both the chairside and portable ambient ACDs were functioning, an estimated effectiveness of 100% in capturing PM10 was achieved. In the MDC, in all conditions where the chairside ACD was used without the negative pressure module, an estimated effectiveness of 100% was also achieved. The simultaneous operation of the negative pressure module in the MDC, which led to a room negative pressure of -0.25 inch wc, reduced the chairside ACD's effectiveness in capturing aerosols. Conversely, the use of the WMAF in the MDC in combination with the chairside ACD further reduced exposure to PM10 below the initial background level. Nonetheless, in all conditions assessed in both settings (dental clinic operatory and MDC), larger visible aerosols were produced, often landing on the surrounding environment. A fair portion of these aerosols landed on the inside of the chairside ACD flange. CONCLUSIONS: This assessment suggests that the use of the tested chairside ACD, by capturing aerosols at the source of generation, had the greatest impact on reducing exposure of dental personnel to PM10 produced during dental procedures. This study also indicates that such exposure is further reduced with the addition of an ambient ACD. However, creating a negative pressure room as high as -0.25 inch wc can lead to air turbulence reducing the effectiveness of ACDs in capturing aerosols at the source. Furthermore, the presence of uncaptured droplets and spatter on the surrounding environment supports the need to complement the use of engineering controls with proper administrative controls and personal protective equipment, as recommended by governmental agencies and the scientific community for preventing the transmission of infection in health care settings.

Novel Temperature-Dependent Development Rate Models for Postdiapause Egg Eclosion of Three Important Arthropod Pests Found in Commercial Christmas Tree Plantations of Southern Québec, Canada.

The balsam twig aphid Mindarus abietinus Koch (Hemiptera: Aphididae), the spruce spider mite Oligonychus ununguis (Jacobi) (Acari: Tetranychidae), and the pine needle scale Chionaspis pinifoliae (Fitch) (Hemiptera: Diaspididae) are three important pests for the Christmas tree industry of Québec, Canada. Temperature-dependent development rates for postdiapause overwintering eggs of these species have never been studied for populations of southern Québec, where the vast majority of Christmas trees are grown. The accumulation of physiological time in growing degree days (GDD) is a standard tool to predict egg eclosion dates for pests, when first generation immatures are most vulnerable to insecticidal control. Development rates for postdiapause eggs were tested at four or five constant temperatures in the 11-23°C range under controlled conditions, based on time before hatching for eggs collected in a balsam fir plantation in late winter. The standard linear model and three published nonlinear models were fitted to the data and compared for their ability to estimate key biological temperature parameters and to predict development rates of postdiapause eggs. Validation of model predictions of egg eclosion time on balsam fir in the field was reasonably accurate using the classical linear model where field-accumulated GDD were calculated with a particular interpretation of the average method based on daily maximum and minimum temperatures. The linear model could predict mean egg eclosion within around 5 d of eclosion dates observed in the field.

A retrospective cohort study of cancer incidence among patients treated with radiosynoviorthesis.

Radiosynoviorthesis (RS) is an intra-articular injection of a radioactive colloid for the treatment of synovitis administered most often to patients with rheumatoid arthritis or haemophilia. Although highly cost-effective in comparison with surgical or arthroscopic synovectomy, the risk of cancer associated with this treatment is not well known. We evaluated the incidence of cancer in a group of patients treated with RS. A cohort of 2412 adult patients with a variety of underlying conditions (mainly rheumatoid arthritis) and treated with at least one RS between January 1976 and December 2001, was recruited from two centres in Montréal. Cancer incidence and mortality data for cohort members over that time period were obtained from regulatory agencies using linkage. Background rates for all and specific types of cancer were obtained for the provincial (Québec) and national (Canada) population according to age, gender and calendar period categories. Category-specific rates in the cohort were compared with rates in similar categories from the general population generating standardized incidence ratios (SIR). The effects of specific isotope doses and of number of RS treatments were analysed using a Cox-regression model. No increase in the risk of cancer was observed (SIR 0.96; 95% confidence interval 0.82-1.12). There was no dose-response relationship with the amount of radioisotope administered or number of RS treatments. The study provides some indication for the safety of the procedure but homogenous diagnostic groups of younger patients (such as haemophilic patients) receiving RS will need more evaluation.

Intravenous immunoglobulin attenuates airway hyperresponsiveness in a murine model of allergic asthma.

BACKGROUND: Intravenous immunoglobulin (IVIG) has potent anti-inflammatory and immune-modulating properties. IVIG has been utilized as a steroid-sparing agent in severe asthma, but the results of clinical trials have been conflicting. OBJECTIVE: To determine whether IVIG is able to attenuate bronchial reactivity, pulmonary inflammation and T cell function using a murine model of allergic airways disease. METHODS: BALB/c or C57BL/6 mice were sensitized to ovalbumin (OVA) or a phosphate-buffered saline control using local nasal sensitization, and then received five intranasal challenges on days 28-32 before sacrifice. Mice were treated intraperitoneally with either IVIG (1-2 g/kg) or equivalent human serum albumin 24 h before the first OVA challenge. Bronchial reactivity to methacholine was examined using the FlexiVent small animal ventilator. We evaluated pulmonary histology, mRNA from lung digests for T-helper type 2 (Th2)-related genes and bronchoalveolar lavage for cell counts and cytokines. Splenocytes were utilized to study OVA-induced cell proliferation, cytokine production and dendritic cell maturation. RESULTS: IVIG markedly attenuated the perivascular and peribronchial pulmonary inflammation, and decreased bronchial hyperresponsiveness to methacholine. IVIG treatment of splenocytes from sensitized animals diminished cellular proliferation to OVA, whereas IVIG treatment in vivo markedly attenuated OVA-driven splenocyte proliferation. This is accompanied by diminished IL-13 and TNF-α levels in splenocyte culture, decreased expression of Jagged-1, increased Delta-4 and decreased GATA-3 mRNA levels, signs that IVIG has suppressed the expected Th2 response that accompanies repeated allergen exposure. Increased regulatory T cells were found in draining pulmonary lymph nodes in IVIG-treated mice but not in controls. CONCLUSIONS AND CLINICAL RELEVANCE: IVIG was effective in ameliorating allergic airway disease in our model. IVIG may be a promising adjunct therapy requiring further study for patients with severe asthma.

Children with atopic histories exhibit impaired lipopolysaccharide-induced Toll-like receptor-4 signalling in peripheral monocytes.

BACKGROUND: The hygiene hypothesis states that early exposure to bacterial products such as lipopolysaccharide (LPS) may be protective against the development of allergic diseases. Whether atopic disease affects the ability of immune cells to respond to LPS is unclear. Our laboratory has demonstrated previously that children express high levels of Toll-like receptor (TLR)-4 on CD4(+) cells in nasal mucosa. OBJECTIVE: To determine if children with a history of allergic disease have impaired responses to LPS on circulating CD4(+) leucocytes. METHODS: Peripheral blood mononuclear cells from children (aged 2-18) and adults with or without a history of atopic conditions were cultured with/without IL-4 or LPS for up to 24 h. Expression of surface TLR-4, CD14, CD4, CD3, as well as of intracellular phosphorylated (p42/p44) ERK and p38 mitogen-activated protein kinase (MAPK) were assessed by flow cytometry. RESULTS: A history of atopy in children was associated with impaired LPS-induced TLR-4-dependent phosphorylation of (p42/44) ERK and p38 MAPK by CD4(+) monocytes. Decreased LPS signalling was reproduced by pre-incubation of control cells with recombinant IL-4. LPS stimulation also decreased TLR-4 expression on monocytes from children without atopic histories but not from atopic subjects. CD4(+) T lymphocytes showed limited LPS responsiveness, regardless of atopic status. In contrast with non-atopic children, TLR-4 expression on monocytes of children with atopic histories decreased as a function of age. CONCLUSIONS: This study provides evidence for defective LPS recognition on circulating CD4(+) leucocytes of subjects with atopic histories compared with those from non-atopic children. CD4(+) TLR4(+) monocytes from children with atopic histories failed to phosphorylate MAPKs. Our results suggest that a history of atopic disease is associated with impaired TLR-4-mediated innate immune function compared with non-atopic children.

B lymphocytes in inflammatory airway diseases.

B lymphocytes are key players in all facets of adaptive immune responses and are responsible for the production of IgE antibodies, initiators of allergic hypersensitivity reactions. Recent evidence indicates that B cells may be a crucial player in allergic and inflammatory airway pathology, directly populating upper and lower airway tissues. This review examines human and animal studies that directly demonstrated the presence of B lymphocytes in airway tissues and elaborates on their function as antibody-secreting cells, antigen-presenting cells and producers of inflammatory and regulatory cytokines. B lymphocytes appear to contribute to multiple facets of immune homeostasis in inflammatory diseases of the upper and lower airways.

A randomized, double-blinded, placebo-controlled trial of pseudocatalase cream and narrowband ultraviolet B in the treatment of vitiligo.

BACKGROUND: Pseudocatalase cream in conjunction with narrowband ultraviolet B (NB-UVB) has previously been reported to result in repigmentation of vitiliginous skin. OBJECTIVES: The purpose of this 24-week, double-blind, placebo-controlled, randomized, single-centre trial was to assess the efficacy of pseudocatalase cream and NB-UVB vs. placebo and NB-UVB for the treatment of vitiligo. METHODS: Patients with active vitiligo on their face and/or hands applied either pseudocatalase cream or placebo to their whole body, twice daily for 24 weeks. NB-UVB therapy was administered three times a week for the duration of the trial. Efficacy was assessed primarily by digital image analysis of photographs. RESULTS: Thirty-two patients were randomized to either the pseudocatalase arm (n = 14) or placebo (n = 18). Between-group analysis did not show a statistically significant improvement in percentage area affected in the pseudocatalase cream group when compared with placebo. However, a statistically significant improvement was found within each group by week 12, which was maintained throughout the study. CONCLUSIONS: NB-UVB treatment is a moderately effective treatment for vitiligo. Pseudocatalase cream does not appear to add any incremental benefit to NB-UVB alone.

[Mother-daughter relationship inventory]. / L'inventaire des relations mère-fille.

The present paper centers on the validation of the French-version of the mother-daughter relationship inventory (MDREL), a self-reported questionnaire developed by Inazu and Fox (1980) and translated by Achim. This nine-item self-reported questionnaire assesses young women's perceptions pertaining to the social-emotional support conveyed by their mother, as well as the overall quality of their mother-daughter relationship. The MDREL is the product of factor analyses conducted on 23 statements concerning young women's perception regarding the following dimensions: presence of an open-communication between the mother and the daughter; presence of uncertainties and ambiguities in the description made by the daughter concerning her relationship with her mother; ambivalence expressed by the daughter in regards to mother-daughter rapprochement and intimacy. This instrument is of great interest as it specifically assesses the perceived quality of the mother-daughter relationship during adolescence, a period in which the mother remains an authority-figure and the daughter's sexuality is activated. A total of 126 young women completed the French-version of this self-reported questionnaire. Results indicate good psychometric properties in both validity and reliability. Factor analyses of the French-version of the MDREL yielded two distinct factors, namely an allo-centered and a self-centered assessment. This French-version of the MDREL named l'Inventaire des relations mère-fille (IRMF) can thus be used in studies that focus on mother-daughter relationships. The problematic overtone present in many items suggests that this instrument can be administered to clinical populations.

[The neurostimulator for brachial plexus blockade by the axillary approach: a metaanalysis on its efficacy to increase the success rate]. / Méta-analyse: intérêt du neurostimulateur dans l'amélioration du taux de succès du bloc axillaire.

OBJECTIVE: To evaluate the effectiveness of the neurostimulator to improve the success rate of a brachial plexus blockade by the axillary approach. STUDY DESIGN: Metaanalysis. METHODS: Ten prospective randomized studies comparing a neurostimulating technique (NST) of brachial plexus blockade performed by the axillary approach to another technique were kept for analysis. A successful block was defined as blockade of the four following nerves: radial, median, ulnar and musculocutaneous. Data were entered on an intention to treat basis and were analyzed with a random model. A p<0.05 was considered significant. RESULTS: Data were heterogenous (p < 0.001) and the Cochran-Mantel-Haenzel test showed that the neurostimulator does not improve the success rate of brachial plexus blocks performed by the axillary approach when all available studies are considered as a whole (p = 1). For the subgroup of studies where four nerves were stimulated however, the NST decreases the incidence of failed block by 25% (95% CI = 7-42%) (p < 0.0001). There were 12 patients with systemic signs of local anesthetics toxicity when a NST was used compared to 28 when it was not (p = 0.04), relative risk of 0.7 (95% CI= 0.6-0.8). CONCLUSION: This study shows that the neurostimulator improves the success rate of brachial plexus blocks performed by the axillary approach only when three nerves or more are stimulated and its use decreases the incidence of systemic local anaesthetics toxicity.

Contextual modulation of synchronization to random dots in the cat visual cortex.

Synchronization of neuronal activity has been proposed as a binding mechanism for integration of image properties into one coherent percept. In the present study, we investigated the contextual modulation of synchronization to random dot patterns. Coherent motion of random dots evoked well synchronized responses in area 17 of anaesthetized cats when the stimulus was presented in the compound receptive field of recorded sites. Gradually changing the directional coherence of random dots in the surround while maintaining fully coherent motion of the stimulus in the receptive field significantly suppressed synchronization of neuronal activity for some stimulus conditions. However, usually one or two peaks of increased synchronization were found in the surround coherence tuning curves with low (8-12%) and/or moderate (25-50%) coherence in the surround. At the population level, synchronization was significantly depressed with incoherent motion in the receptive field and when both the surround and the receptive field were jointly stimulated with 0% coherence. The intriguing finding was the discovery of two distinct groups of cells with opposite synchronization changes dependent on the presence or absence of significant synchronization in their spontaneous activity. The latter group of neurons showed peaks of increased synchronization with lower surround coherence, thus probably being more sensitive to the direction of the surround motion. Overall, our findings support the notion that binding of stimulus properties can be achieved by synchronized activity of cortical cells. However, our findings go further than the original hypothesis of feature binding by synchrony to show that synchronization of cortical activity may be directly related to the decision making processes, which in turn are related to the threshold of perception of coherent motion.

Activation of the renin-angiotensin system contributes significantly to the pathophysiology of oliguria in patients undergoing posterior spinal fusion.

BACKGROUND AND OBJECTIVE: This study was undertaken to investigate the role played by antidiuretic hormone (ADH), the renin-angiotensin system and atrial natriuretic factor (ANF) in the oliguria in patients undergoing spinal fusion. METHODS: Sixteen patients undergoing posterior spinal fusion using isoflurane and fentanyl (n = 8) or sufentanil (n = 8) had renin, aldosterone, ADH and ANF measurements. RESULTS: Compared to the non-oliguric patients, the oliguric patients had a higher number of fused vertebrae 10.5 +/- 1.3 vs. 9.0 +/- 0.5 (P = 0.01) and higher renin values at 12h (3.3 +/- 3.2 vs. 0.7 +/- 0.6 ng L(-1) s(-1), P = 0.04). Hormonal values that had a significant correlation with intraoperative diuresis were: renin at 0.5 h (r2 = 0.26, P = 0.04), aldosterone at 0.5 h (r2 = 0.30, P = 0.03) and ANF at 0.5 h (r2 = 0.32, P = 0.02). Those that had a significant correlation with the mean postoperative diuresis were: renin at 6 h (r2 = 0.29, P = 0.03), 8h (r2 = 0.26, P = 0.04) and 12h (r2 = 0.31, P = 0.03), aldosterone at 6h (r2 = 0.54, P = 0.001), 8h (r2 = 0.40, P = 0.01) and 12h (r2 = 0.32, P = 0.03), ADH at 24h (r2 = 0.38, P = 0.01) and ANF at 6h (r2 = 0.26, P = 0.045). Using stepwise regression, excluding hormonal values, only two continuous variables had a significant correlation with the mean postoperative diuresis: the number of fused vertebrae (P = 0.02) and the length of surgery (P = 0.02). CONCLUSION: Activation of the renin-angiotensin system is the major cause of the early intraoperative oliguria. ADH and the renin-angiotensin system are both involved in the pathophysiology of postoperative oliguria in patients undergoing spinal fusion.

Cardiopulmonary bypass induces significant platelet activation in children undergoing open-heart surgery.

BACKGROUND AND OBJECTIVES: To evaluate the effects of cardiopulmonary bypass (CPB) on platelet function in children undergoing open-heart surgery. METHODS: Data from 16 consecutive children undergoing cardiac surgery with CPB were prospectively collected. Blood samples of 10 mL were collected via the central venous line immediately before and after CPB for CD62 measurements by flow cytometry. RESULTS: Ten children had acyanotic heart disease (median age 3 yr, range 1.8-14) and six had a cyanotic defect (median age 4yr, range 2-14). The platelet count decreased significantly with CPB in both groups: from 163.5 (130-201) to 93.5 (57-186) x 10(3) microL(-1) in acyanotic children and from 139.5 (77-212) to 75 (43-99) x 10(3) microL(-1) in cyanotic children (P < 0.0001). The percentage of activated platelets was significantly lower in acyanotic children at baseline: 1% (0-23%) vs. 5% (3-8%) (P = 0.07). CPB increased the percentage of activated platelets significantly in both groups: post-bypass the values were 10% (range 1-17%) in acyanotic children and 7% (range 1-30%) in cyanotic children (P = 0.03). The increase in the percentage of activated platelets did not differ between the two study groups (P = 0.11). CONCLUSION: CPB induces significant platelet activation in children undergoing open-heart surgery.

Victim-choice polymorphia among serious sex offenders.

The victim-choice polymorphia of 178 sexual aggressors divided into six subtypes, incest offenders, pseudoincest offenders, sexual aggressors of familiar children, sexual aggressors of unfamiliar children, sexual aggressors of familiar women, and sexual aggressors of unfamiliar women, was compared. Results showed that sex offenders remained stable in their choice of victim from one offence to another in terms of victim age, victim gender, and aggressor-victim relationship. Subjects characterised by high levels of polymorphia were pseudoincest offenders and sexual aggressors of familiar women, whereas sexual aggressors of both unfamiliar women and unfamiliar children were characterised by low levels of polymorphia. Recommendations regarding how to further refine sex offender typologies are discussed.

Haemostatic disorders during liver transplantation.

Profound and complex coagulation disorders are encountered during liver transplantation. They include preoperative coagulation disorders related to the liver disease and haemostatic changes related to the procedure itself. They commonly lead to increased intraoperative bleeding, especially due to increased fibrinolysis, the contribution of which can be demonstrated by the relative efficacy of antifibrinolytics. Given the multifactorial nature of bleeding in liver transplantation, preoperative coagulation tests cannot predict blood loss even if some statistical relationship is occasionally found. Preoperative correction of coagulation defects has not been shown to be effective in reducing intraoperative bleeding. Throughout the procedure, a rapid and sensitive method for monitoring coagulation is necessary in order to guide the rational use of blood components and pharmacological agents. The usefulness of such a method to assist management of blood loss or blood component requirements is poorly documented and controversial.

Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2.

We report here the preclinical profile of etoricoxib (MK-0663) [5-chloro-2-(6-methylpyridin-3-yl)-3-(4-methylsulfonylphenyl) pyridine], a novel orally active agent that selectively inhibits cyclooxygenase-2 (COX-2), that has been developed for high selectivity in vitro using whole blood assays and sensitive COX-1 enzyme assays at low substrate concentration. Etoricoxib selectively inhibited COX-2 in human whole blood assays in vitro, with an IC(50) value of 1.1 +/- 0.1 microM for COX-2 (LPS-induced prostaglandin E2 synthesis), compared with an IC(50) value of 116 +/- 8 microM for COX-1 (serum thromboxane B2 generation after clotting of the blood). Using the ratio of IC(50) values (COX-1/COX-2), the selectivity ratio for the inhibition of COX-2 by etoricoxib in the human whole blood assay was 106, compared with values of 35, 30, 7.6, 7.3, 2.4, and 2.0 for rofecoxib, valdecoxib, celecoxib, nimesulide, etodolac, and meloxicam, respectively. Etoricoxib did not inhibit platelet or human recombinant COX-1 under most assay conditions (IC(50) > 100 microM). In a highly sensitive assay for COX-1 with U937 microsomes where the arachidonic acid concentration was lowered to 0.1 microM, IC(50) values of 12, 2, 0.25, and 0.05 microM were obtained for etoricoxib, rofecoxib, valdecoxib, and celecoxib, respectively. These differences in potency were in agreement with the dissociation constants (K(i)) for binding to COX-1 as estimated from an assay based on the ability of the compounds to delay the time-dependent inhibition by indomethacin. Etoricoxib was a potent inhibitor in models of carrageenan-induced paw edema (ID(50) = 0.64 mg/kg), carrageenan-induced paw hyperalgesia (ID(50) = 0.34 mg/kg), LPS-induced pyresis (ID(50) = 0.88 mg/kg), and adjuvant-induced arthritis (ID(50) = 0.6 mg/kg/day) in rats, without effects on gastrointestinal permeability up to a dose of 200 mg/kg/day for 10 days. In squirrel monkeys, etoricoxib reversed LPS-induced pyresis by 81% within 2 h of administration at a dose of 3 mg/kg and showed no effect in a fecal 51Cr excretion model of gastropathy at 100 mg/kg/day for 5 days, in contrast to lower doses of diclofenac or naproxen. In summary, etoricoxib represents a novel agent that selectively inhibits COX-2 with 106-fold selectivity in human whole blood assays in vitro and with the lowest potency of inhibition of COX-1 compared with other reported selective agents.

Cloning, expression, and up-regulation of inducible rat prostaglandin e synthase during lipopolysaccharide-induced pyresis and adjuvant-induced arthritis.

We have cloned and expressed the inducible form of prostaglandin (PG) E synthase from rat and characterized its regulation of expression in several tissues after in vivo lipopoylsaccharide (LPS) challenge. The rat PGE synthase is 80% identical to the human enzyme at the amino acid level and catalyzes the conversion of PGH(2) to PGE(2) when overexpressed in Chinese hamster ovary K1 (CHO-K1) cells. PGE synthase activity was measured using [(3)H]PGH(2) as substrate and stannous chloride to terminate the reaction and convert all unreacted unstable PGH(2) to PGF(2alpha) before high pressure liquid chromatography analysis. We assessed the induction of PGE synthase in tissues from Harlan Sprague-Dawley rats after LPS-induced pyresis in vivo. Rat PGE synthase was up-regulated at the mRNA level in lung, colon, brain, heart, testis, spleen, and seminal vesicles. Cyclooxygenase (COX)-2 and interleukin 1beta were also up-regulated in these tissues, although to different extents than PGE synthase. PGE synthase and COX-2 were also up-regulated to the greatest extent in a rat model of adjuvant-induced arthritis. The RNA induction of PGE synthase in lung and the adjuvant-treated paw correlated with a 3.8- and 16-fold induction of protein seen in these tissues by immunoblot analysis. Because PGE synthase is a member of the membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) family, of which leukotriene (LT) C(4) synthase and 5-lipoxygenase-activating protein are also members, we tested the effect of LTC(4) and the 5-lipoxygenase-activating protein inhibitor MK-886 on PGE synthase activity. LTC(4) and MK-886 were found to inhibit the activity with IC(50) values of 1.2 and 3.2 microm, respectively. The results demonstrate that PGE synthase is up-regulated in vivo after LPS or adjuvant administration and suggest that this is a key enzyme involved in the formation of PGE(2) in COX-2-mediated inflammatory and pyretic responses.

Potency and selectivity of inhibition of cathepsin K, L and S by their respective propeptides.

The prodomains of several cysteine proteases of the papain family have been shown to be potent inhibitors of their parent enzymes. An increased interest in cysteine proteases inhibitors has been generated with potential therapeutic targets such as cathepsin K for osteoporosis and cathepsin S for immune modulation. The propeptides of cathepsin S, L and K were expressed as glutathione S-transferase-fusion proteins in Escherichia coli. The proteins were purified on glutathione affinity columns and the glutathione S-transferase was removed by thrombin cleavage. All three propeptides were tested for inhibitor potency and found to be selective within the cathepsin L subfamily (cathepsins K, L and S) compared with cathepsin B or papain. Inhibition of cathepsin K by either procathepsin K, L or S was time-dependent and occurred by an apparent one-step mechanism. The cathepsin K propeptide had a Ki of 3.6-6.3 nM for each of the three cathepsins K, L and S. The cathepsin L propeptide was at least a 240-fold selective inhibitor of cathepsin K (Ki = 0.27 nM) and cathepsin L (Ki = 0.12 nM) compared with cathepsin S (Ki = 65 nM). Interestingly, the cathepsin S propeptide was more selective for inhibition of cathepsin L (Ki = 0.46 nM) than cathepsin S (Ki = 7.6 nM) itself or cathepsin K (Ki = 7.0 nM). This is in sharp contrast to previously published data demonstrating that the cathepsin S propeptide is equipotent for inhibition of human cathepsin S and rat and paramecium cathepsin L [Maubach, G., Schilling, K., Rommerskirch, W., Wenz, I., Schultz, J. E., Weber, E. & Wiederanders, B. (1997), Eur J. Biochem. 250, 745-750]. These results demonstrate that limited selectivity of inhibition can be measured for the procathepsins K, L and S vs. the parent enzymes, but selective inhibition vs. cathepsin B and papain was obtained.

[The forgotten actors]. / Les acteurs oubliés.

Within the Regional Plans for the Organization of Services, Quebec's mental health reform has tried to redistribute power and influence to mutual aid groups for consumers and their families. However, it has failed to provide them with the financial resources that would allow them to exert that new power. The groups don't have enough personnel to fill the decision-making positions accorded to them under the regional plans while, at the same time, continuing to provide services to consumers. Real partnership requires equality in resources. Social integration being the product of an interaction between consumers and citizens, citizens are the forgotten actors of the interaction. We fail to support them when they are faced with behaviours that they find strange and disturbing. Attitudinal and behavioural changes are interrelated and concomitant; that is, the transformation of citizens' prejudice into acceptance is helped by consumers' efforts to adopt less offensive behaviours.