Midbrain serotonergic neurons are central pH chemoreceptors

Serotonergic neurons in the medulla are central respiratory chemoreceptors. Here we show that serotonergic neurons in the midbrain of rats are also highly chemosensitive to small changes in CO2/pH and are closely associated with large penetrating arteries. We propose that midbrain raphé neurons are sensors of blood CO2 that maintain pH homeostasis by inducing arousal, anxiety and changes in cerebrovascular tone in response to respiratory acidosis.     

The effect of indocyanine-green on functional outcome of macular pucker surgery

PURPOSE: To compare functional results after surgery for macular pucker either with or without indocyanine-green staining of the internal limiting membrane (ILM) and to evaluate the ultrastructure of the tissue removed. DESIGN: Retrospective analysis of two successive, consecutive, interventional case series. METHODS: Functional outcome (visual acuity, Goldmann perimetry) of 48 eyes of 48 consecutive patients with (group 1, n = 20) or without (group 2, n = 28) intraoperative use of indocyanine-green (ICG) was retrospectively analyzed. For statistical analysis, best-corrected visual acuity measured at the last presentation was considered. Only patients with an idiopathic macular pucker were included. Surgery consisted of three-port pars plana vitrectomy, and removal of epiretinal tissue and the ILM in a second step. Commercially available ICG with a concentration of.05% and an osmolarity of 275 mOsm was used to stain the ILM. The surgical technique used for both groups was identical, except the use of ICG. Epiretinal tissue of all eyes was harvested and prepared for ultrastructural analysis using light and electron microscopy. RESULTS: Follow-up time was 8.5 months in group 1 and 5.4 months in group 2. Whereas patients operated on without ICG experienced a significant improvement of median best-corrected visual acuity from 20/63 (range, 20/400 to 20/32) preoperatively to 20/40 (range, 20/200 to 20/25) postoperatively (P < .001), median best-corrected visual acuity remained 20/63 before (range, 20/200 to 20/63) and after (range, 20/400 to 20/20) (P > .9) ICG-assisted peeling. There was a statistically significant difference (P = .013) in best-corrected postoperative visual acuity of patients with and without the use of ICG. An improvement of vision was noted in 86% of patients without and 55% of patients with ICG-assisted surgery. Thirty-five percent of patients after ICG application presented with a deterioration of visual acuity. Furthermore, we observed large visual field defects in 7 of 20 patients after ILM staining. No visual field defects were noted after conventional peeling. Histologic analysis revealed clear differences between the two groups concerning the amount of cellular elements adjacent to the retinal surface of the ILM: There was more cellular debris visible in specimens after ICG application during surgery. Additionally, in contrast to surgery without ILM staining, epiretinal cells had ruptured and lost their cellular integrity after ICG-assisted vitrectomy. CONCLUSIONS: Indocyanine green-assisted surgery for macular pucker might have an adverse effect on functional outcome. Although there were obvious differences in the ultrastructure of tissue removed during surgery, our observations cannot be explained by histologic analysis alone. Other, so far unknown mechanisms of action must be considered.     

Can a practicing surgeon detect early lymphedema reliably?

BACKGROUND: Lymphedema may be identified by simpler circumference changes as compared with changes in limb volume. METHODS: Ninety breast cancer patients were prospectively enrolled in an academic trial, and seven upper extremity circumferences were measured quarterly for 3 years. A 10% volume increase or greater than 1 cm increase in arm circumference identified lymphedema with verification by a lymphedema specialist. Sensitivity and specificity of several different criteria for detecting lymphedema were compared using the academic trial as the standard. RESULTS: Thirty-nine cases of lymphedema were identified by the academic trial. Using a 10% increase in circumference at two sites as the criterion, half the lymphedema cases were detected (sensitivity 37%). When using a 10% increase in circumference at any site, 74.4% of cases were detected (sensitivity 49%). Detection by a 5% increase in circumference at any site was 91% sensitive. CONCLUSIONS: An increase of 5% in circumference measurements identified the most potential lymphedema cases compared with an academic trial.     

Intrathecally applied flurbiprofen produces an endocannabinoid-dependent antinociception in the rat formalin test

It is generally accepted that the phospholipase-A2-cyclooxygenase-prostanoids-cascade mediates spinal sensitization and hyperalgesia. However, some observations are not in line with this hypothesis. The aim of the present work was to investigate whether different components of this cascade exhibit nociceptive or antinociceptive effects in the rat formalin test. Intrathecal (i.th.) injection of prostaglandin E2 (PGE2) induced a dose-dependent antinociceptive effect on the formalin-induced nociception. Furthermore, thimerosal, which inhibits the reacylation of arachidonic acid thereby enhancing arachidonic acid levels, had an antinociceptive effect rather than the expected pronociceptive effect when given i.th. While the phospholipase A2 inhibitor methyl arachidonyl fluorophosphonate (MAFP; i.th.) had a significant antinociceptive effect, its analogue palmitoyl trifluoromethyl ketone (PTFMK; i.th.) had no significant effect on the formalin-induced nociception. However, MAFP, but not PTFMK, showed a cannabinoid CB1 agonistic effect as shown by the inhibition of electrically evoked contractions of the vas deferens isolated from CB1 wild-type mice but not of that from CB1 knockout mice. The antinociceptive effect of MAFP was completely reversed by the CB1 receptor antagonist AM-251 (i.th.), thus attributing such effect to its CB1 agonistic effect. Moreover, the antinociceptive effect of the cyclooxygenase inhibitor, flurbiprofen (i.th.) was reversed by the co-administration of AM-251, but not by PGE2. Finally. the combination of phenylmethylsulfonyl fluoride (PMSF; intraperitoneal), which inhibits the degradation of anandamide through the inhibition of fatty acid amidohydrolase, with thimerosal (i.th.) produced a profound CB1-dependent antinociception. The present results show that endocannabinoids play a major role in mediating flurbiprofen-induced antinociception at the spinal level.     

Präsentismus vermeiden – Arbeitsbereitschaft fördern. Ein Zielkonflikt der Pandemieplanung?

Introduction

Employees are recommended to stay at home when they show symptoms of an acute respiratory infection. Yet, in case of an influenza pandemic another challenge is to promote the employees’ high willingness to report to work. For pandemic planning this raises the question, whether there is a conflict between these two goals.

Method

Employee survey at the urban administration of Dortmund, Germany, about presenteeism with symptoms of an acute respiratory infection and the willingness to report to work during an influenza pandemic.

Results

Results of multivariate linear regression indicated: There is only little association between propensity for presenteeism with symptoms of an acute respiratory infection and willingness to report to work during an influenza pandemic (R²?=?0,024).

Conclusion

Results did not support the aforementioned conflict of goals between reducing presenteeism with symptoms of an acute respiratory infection and promoting willingness to report to work during an influenza pandemic. Further research should investigate interventions, which will support both goals alike, in order to support pandemic planning.     

Purchasing Behavior,Setting, Pricing,Family: Determinants of School Lunch Participation

Despite growing school lunch availability in Germany, its utilization is still low, and students resort to unhealthy alternatives. We investigated predictors of school lunch participation and reasons for nonparticipation in 1215 schoolchildren. Children reported meal habits, parents provided family-related information (like socioeconomic status), and anthropometry was conducted on-site in schools. Associations between school lunch participation and family-related predictors were estimated using logistic regression controlling for age and gender if necessary. School was added as a random effect. School lunch participation was primarily associated with family factors. While having breakfast on schooldays was positively associated with school lunch participation (OR_adj = 2.20, p = 0.002), lower secondary schools (OR_adj = 0.52, p < 0.001) and low SES (OR_adj = 0.25, p < 0.001) were negatively associated. The main reasons for nonparticipation were school- and lunch-related factors (taste, time constraints, pricing). Parents reported pricing as crucial a reason as an unpleasant taste for nonparticipation. Nonparticipants bought sandwiches and energy drinks significantly more often on school days, whereas participants were less often affected by overweight (OR = 0.66, p = 0.043). Our data stress school- and lunch-related factors as an important opportunity to foster school lunch utilization.     

Estimation of dietary intake of bis(2-ethylhexyl)phthalate (DEHP) by consumption of food in the German population

In the study presented here, we evaluated the exposure of the German population aged 14–80 years to bis(2-ethylhexyl)phthalate (DEHP) from consumption of food by means of deterministic and probabilistic estimations. The study was performed on the basis of an extensive review of literature from around the world reporting measured data on DEHP in food, as well as official German food control data. Only data from individual measurements were considered and used for fitting of distributions. A wide range of concentrations in non-representative samples are reported in the literature. On the basis of the available DEHP concentration data, 37 food categories were characterized which covered all major food classes. Food consumption data were taken from the diet history interviews of the German National Nutrition Survey II (Nationale Verzehrsstudie II) which was performed in 2005/2006 in a representative study population of 15,371 and is the most recent data source of this kind in Germany. Average DEHP intake was estimated deterministically using data on measured concentrations in food (medians and means) and food consumption (means). A total dietary exposure to DEHP of 3.6 (median based) and 9.3 μg/kg of BW per day (based on mean values) was estimated deterministically. In addition, distributions of both concentrations and consumption figures were fitted using the @RISK best fit tool for further probabilistic estimations. This approach resulted in estimates within the same range: the estimated median DEHP intake in the whole population (both non-consumers and consumers of the foods considered) was 10.2, the arithmetic mean 14.0 and the 95th percentile 28.6 μg/kg of BW per day. The respective estimates for consumers only were 12.4, 18.7 and 36.5 μg/kg of BW per day. These results demonstrate that the probabilistic approach is able to estimate broader ranges of exposure even when using data representing an average intake. Moreover, it reflects the uncertainties of the estimation due to insufficient analytical data on concentrations of DEHP in food.     

Intake of aspirin prior to metamizole does not completely prevent high on treatment platelet reactivity

European Journal of Clinical Pharmacology - Metamizole can sterically inhibit aspirin (ASA) from binding to cyclooxygenase 1 (COX1). It is recommended that ASA should be taken 30 min prior to...     

Interactions of Bordetella pertussis adenylyl cyclase toxin CyaA with calmodulin mutants and calmodulin antagonists: comparison with membranous adenylyl cyclase I

The adenylyl cyclase (AC) toxin CyaA from Bordetella pertussis constitutes an important virulence factor for the pathogenesis of whooping cough. CyaA is activated by calmodulin (CaM) and compromises host defense by excessive cAMP production. Hence, pharmacological modulation of the CyaA/CaM interaction could constitute a promising approach to treat whooping cough, provided that interactions of endogenous effector proteins with CaM are not affected. As a first step toward this ambitious goal we examined the interactions of CyaA with wild-type CaM and four CaM mutants in which most methionine residues were replaced by leucine residues and studied the effects of the CaM antagonists calmidazolium, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). CyaA/CaM interaction was monitored by CaM-dependent fluorescence resonance energy transfer (FRET) between tryptophan residues in CyaA and 2'-(N-methylanthraniloyl)-3'-deoxy-adenosine 5'-triphosphate and catalytic activity. Comparison of the concentration/response curves of CaM and CaM mutants for FRET and catalysis revealed differences, suggesting a two-step activation mechanism of CyaA by CaM. Even in the absence of CaM, calmidazolium inhibited catalysis, and it did so according to a biphasic function. Trifluoperazine and W-7 did not inhibit FRET or catalysis. In contrast to CyaA, some CaM mutants were more efficacious than CaM at activating membranous AC isoform 1. The slope of CyaA activation by CaM was much steeper than of AC1 activation. Collectively, the two-step activation mechanism of CyaA by CaM offers opportunities for pharmacological intervention. The failure of classic CaM inhibitors to interfere with CyaA/CaM interactions and the different interactions of CaM mutants with CyaA and AC1 point to unique CyaA/CaM interactions.