New insights into the mechanisms of the vasorelaxant effects of apocynin in rat thoracic aorta

Apocynin is a naturally occurring acetophenone widely used as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Recent data suggested that apocynin might exert NADPH oxidase‐independent pharmacological properties. Among them, vasorelaxant properties have been described, but the mechanisms still give rise to debates. The present study investigated the mechanisms involved in the vasorelaxant effect of apocynin on the in vitro model of rat isolated thoracic aortic rings. Apocynin (30 μm to 10 mm ) induced a dose‐dependent relaxation in both endothelium‐intact and endothelium‐denuded aortic rings with respective EC₅₀ values of 0.78 ± 0.08 and 1.91 ± 0.21 mm . Endothelium removal or inhibition of nitric oxide (NO) synthase with N^ω‐nitro‐l ‐arginine‐methyl ester (l ‐NAME) significantly decreased but did not abolish the effect of apocynin. By contrast, apocynin‐induced relaxation was unchanged after incubation with indomethacin or charybdotoxin plus apamin. In endothelium‐denuded aortas, the vasorelaxant effect of apocynin was significantly reduced by glibenclamide but not by 4‐aminopyridine nor by iberiotoxin. Apocynin significantly decreased Ca²⁺‐induced contraction and inhibited intracellular Ca²⁺mobilization after contraction with phenylephrine. Finally, the acute intravenous injection of apocynin led to an immediate and transient hypotensive effect in spontaneously hypertensive rats (SHR). In conclusion, our data demonstrated that apocynin induces both endothelium‐independent relaxant effects involving inhibition of Ca²⁺mobilization and activation of K_ATP channels in vascular smooth muscle cells and endothelium‐dependent effects mediated by NO. These results should provide a basis for caution when interpreting results on the vascular effects of apocynin.     

Large Cohort Study of Central Venous Catheter Thrombosis during Intravenous Antibiotic Therapy

The frequency and risk factors for central venous catheter-related thrombosis (CRT) during prolonged intravenous (i.v.) antibiotic therapy have rarely been reported. The primary objective of this study was to evaluate the frequency, incidence, and risk factors for CRT among patients being treated with prolonged i.v. antibiotic therapy. The secondary objective was to describe the clinical manifestations, diagnostic evaluation, and clinical management. This cohort study was conducted between August 2004 and May 2010 in a French referral center for osteoarticular infections. All patients treated for bone and joint infections with i.v. antimicrobial therapy through a central venous catheter (CVC) for ≥2 weeks were included. Risk factors were identified using nonparametric tests and logistic regression. A case-control study investigated the role of vancomycin and catheter malposition. A total of 892 patients matched the inclusion criteria. CRT developed in 16 infections occurring in 16 patients (incidence, 0.39/1,000 catheter days). The median time to a CRT was 29 days (range, 12 to 48 days). Local clinical signs, fever, and secondary complications of CRT were present in 15, 8, and 4 patients, respectively. The median C-reactive protein level was 95 mg/liter. The treatment combined catheter removal and a median of 3 months (1.5 to 6 months) of anticoagulation therapy. The outcome was good in all patients, with no recurrence of CRT. Three risk factors were identified by multivariate analysis: male sex (odds ratio [OR], 5.4; 95% confidence interval [CI], 1.1 to 26.6), catheter malposition (OR, 5.3; 95% CI, 1.6 to 17.9), and use of vancomycin (OR, 22.9; 95% CI, 2.8 to 188). Catheter-related thrombosis is a rare but severe complication in patients treated with prolonged antimicrobial therapy. Vancomycin use was the most important risk factor identified.     

What are the factors that influence the attainment of satisfactory energy intake in pediatric intensive care unit patients receiving enteral or parenteral nutrition?

ObjectiveChildren admitted to the intensive care unit (ICU) are at risk of inadequate energy intake. Although studies have identified factors contributing to an inadequate energy supply in critically ill children, they did not take into consideration the length of time during which patients received their estimated energy requirements after having achieved a satisfactory energy intake. This study aimed to identify factors associated with the non-attainment of estimated energy requirements and consider the time this energy intake is maintained.MethodsThis was a prospective study involving 207 children hospitalized in the ICU who were receiving enteral and/or parenteral nutrition. The outcome variable studied was whether 90% of the estimated basal metabolic rate was maintained for at least half of the ICU stay (satisfactory energy intake). The exposure variables for outcome were gender, age, diagnosis, use of vasopressors, malnutrition, route of nutritional support, and Pediatric Index of Mortality and Pediatric Logistic Organ Dysfunction scores.ResultsSatisfactory energy intake was attained by 20.8% of the patients, within a mean time of 5.07 ± 2.48 d. In a multivariable analysis, a diagnosis of heart disease (odds ratio 3.62, 95% confidence interval 1.03–12.68, P = 0.045) increased the risk of insufficient energy intake, whereas malnutrition (odds ratio 0.43, 95% confidence interval 0.20–0.92, P = 0.030) and the use of parenteral nutrition (odds ratio 0.34, 95% confidence interval 0.15–0.77, P = 0.001) were protective factors against this outcome.ConclusionA satisfactory energy intake was reached by a small proportion of patients during their ICU stay. Heart disease was an independent risk factor for the non-attainment of satisfactory energy intake, whereas malnutrition and the use of parenteral nutrition were protective factors against this outcome.     

A pilot project of school‐based intervention integrating drama and language awareness

Background: To help immigrant and refugee adolescents experiencing a severe academic delay cope with adversity, a school‐based intervention combining drama workshops and language awareness activities was piloted in two classrooms. Method: A qualitative analysis of participant observations was performed and the Strength and Difficulty Questionnaire and its Impairment Supplement was administered before and after the intervention. The observations were carried out in two Montreal high schools serving an underprivileged neighbourhood of immigrants, involving two classrooms of underschooled adolescents (n = 27) and two classes of similarly underschooled adolescents chosen among other teachers interested in the intervention, who accepted to participate as a comparison group (n = 28). Results: The adolescents shared their experiences of adversity and felt empowered by the workshops. Self‐reported impairment decreased in the intervention groups. Conclusion: The protective effect of creative language activities for immigrant and refugee youth should be further investigated.     

Calcium inhibits promotion by hot dog of 1,2‐dimethylhydrazine‐induced mucin‐depleted foci in rat colon

Epidemiology suggests that processed meat is associated with colorectal cancer risk, but few experimental studies support this association. We have shown that a model of cured meat made in a pilot workshop promotes preneoplastic lesions, mucin‐depleted foci (MDF) in the colon of rats. This study had two aims: to check if real store‐bought processed meats also promote MDF, and to test if calcium carbonate, which suppresses heme‐induced promotion, can suppress promotion by processed meat. A 14‐day study was done to test the effect of nine purchased cured meats on fecal and urinary biomarkers associated with heme‐induced carcinogenesis promotion. Fecal water from rats given hot dog or fermented raw dry sausage was particularly cytotoxic. These two cured meats were thus given to rats pretreated with 1,2‐dimethylhydrazine, to evaluate their effect on colorectal carcinogenesis. After a 100‐days feeding period, fecal apparent total N‐nitroso compounds (ATNC) were assayed and colons were scored for MDF. Hot dog diet increased fecal ATNC and the number of MDF per colon compared with the no‐meat control diet (3.0 ± 1.7 vs. 1.2 ± 1.4, p < 0.05). In a third study, addition of calcium carbonate (150 µmol/g) to the hot dog diet decreased the number of MDF/colon and fecal ATNC compared with the hot dog diet without calcium carbonate (1.2 ± 1.1 vs. 2.3 ± 1.4, respectively, p < 0.05). This is the first experimental evidence that a widely consumed processed meat promotes colon carcinogenesis in rats. It also shows that dietary prevention of this detrimental effect is possible.     

Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study

OBJECTIVE: To investigate the value of serum antitissue transglutaminase IgA antibodies (IgA-TTG) and IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of coeliac disease in cohorts from different geographical areas in Europe. The setting allowed a further comparison between the antibody results and the conventional small-intestinal histology. METHODS: A total of 144 cases with coeliac disease [median age 19.5 years (range 0.9-81.4)], and 127 disease controls [median age 29.2 years (range 0.5-79.0)], were recruited, on the basis of biopsy, from 13 centres in nine countries. All biopsy specimens were re-evaluated and classified blindly a second time by two investigators. IgA-TTG were determined by ELISA with human recombinant antigen and IgA-EMA by an immunofluorescence test with human umbilical cord as antigen. RESULTS: The quality of the biopsy specimens was not acceptable in 29 (10.7%) of 271 cases and a reliable judgement could not be made, mainly due to poor orientation of the samples. The primary clinical diagnosis and the second classification of the biopsy specimens were divergent in nine cases, and one patient was initially enrolled in the wrong group. Thus, 126 coeliac patients and 106 controls, verified by biopsy, remained for final analysis. The sensitivity of IgA-TTG was 94% and IgA-EMA 89%, the specificity was 99% and 98%, respectively. CONCLUSIONS: Serum IgA-TTG measurement is effective and at least as good as IgA-EMA in the identification of coeliac disease. Due to a high percentage of poor histological specimens, the diagnosis of coeliac disease should not depend only on biopsy, but in addition the clinical picture and serology should be considered.     

Interleukin-2 and natural killer activity in acute type B hepatitis

Natural killer (NK) cell activity against K562 cell line, and interleukin-2 (IL-2) activity in supernatants from lectin-activated PBMC cultures from 17 patients with acute hepatitis B in the early phase of illness were studied. These patients showed enhanced NK cytotoxicity and higher levels of IL2 activity as compared with control subjects. There was a positive correlation between cytotoxicity values and levels of IL2 activity. Furthermore, in the recovery phase of illness there was a tendency towards normalization in both parameters. When patients were divided in accordance with markers of HBV replication, HBV-DNA positive patients showed increased NK cell activity and IL2 levels as compared with the control group, whereas in HBV-DNA-negative patients no differences were found. However, no differences were found between patients with HBeAg and patients with anti-HBe. These results suggest that natural cytotoxicity is increased early in the course of acute hepatitis B, while NK cell activity returns to normal later, during convalescence. Enhanced NK cell activity appears to be secondary, at least in part, to increased production of IL2. Natural cytotoxicity may be one mechanism that controls the HBV infection before other cytotoxic mechanisms become fully operative.     

Resistance to reinfection in experimental murine schistosomiasis: role of porto-hepatic hemodynamics

Experiments were conducted to evaluate critically, and independently of the immune system, the possible role of hemodynamic mechanisms in resistance to schistosomal reinfection. The effects of a challenge schistosomal infection were compared in groups of mice which were either previously infected with schistosomiasis, vaccinated with irradiated cercariae, or underwent partial portal vein ligation for the induction of portal hypertension and porto-systemic shunting. Following infection with 60 cercariae, the appearance of portal hypertension preceded by approximately 2 weeks the development of porto-systemic shunting, which reached maximal values 11 weeks postinfection. Such a primary infection conferred on C3H mice an estimated 90% protection to a 2nd infection, measured by the reduction of worm burden. Worm burdens were also reduced in vaccinated and ligated animals as compared to normal controls. The protection amounted to 30% and 56%, respectively, in the C3H strain and 63% and 75-85%, respectively, in the C57Bl/6 strain. Reduction in worm burden in the ligated animals is believed to be due to the extrahepatic porto-systemic vascular shunts. Hemodynamic as well as immunological factors may account for the resistance to reinfection observed in chronic murine schistosomiasis.