Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

<p>Abstract</p> <p>Background</p> <p>Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 μg·m^-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY).</p> <p>Methods</p> <p>Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF).</p> <p>Results</p> <p>Increased BP and heart rate (HR) by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors – except hemeoxygenase-1 – were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma.</p> <p>Conclusion</p> <p>Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.</p

Nonsurgical and surgical periodontal therapy in single-rooted teeth

The purpose of this study was to compare the effect of tooth related and patient related factors on the success of non-surgical and surgical periodontal therapy. In 41 patients (22 female) with untreated and/or recurrent periodontitis, no therapy, scaling and root planing (SRP), or access flap (AF) were assigned according to probing pocket depth (PPD). PPD and vertical relative attachment level (RAL-V) were obtained initially, 3 and 6 months after therapy. Baseline data were compared according to therapy, jaw, tooth type, and site. Factors influencing clinical parameters were identified using multilevel analyses. Baseline PPDs were deeper interproximally, in the maxilla and at premolars compared to buccal/oral sites, mandibular, and anterior teeth. At 6 months, PPD reduction and RAL-V gain were significantly greater at sites receiving SRP and AF as compared to untreated sites (p < 0.001). PPD reduction and RAL-V gain were significantly less (p < 0.005) in smokers as compared to nosmokers and at interproximal sites (p < 0.0001) as compared to buccal/oral sites. RAL-V gain was less in aggressive periodontitis, and PPD reduction was less in the maxilla (p < 0.001). In sites with greater bone loss and infrabony defects, a poorer response was observed regarding RAL-V gain or PPD reduction, respectively. The conclusions of the study are the following: (1) Nonsurgical and surgical periodontal therapies are effective in single-rooted teeth; (2) severe interproximal bone loss and infrabony defects deteriorate clinical results; and (3) there seem to be more defect-associated (tooth, site) factors influencing treatment outcome than patient-associated factors

Enhancement of endogenous neurogenesis in ephrin-B3 deficient mice after transient focal cerebral ischemia

Cerebral ischemia stimulates endogenous neurogenesis. However, the functional relevance of this phenomenon remains unclear because of poor survival and low neuronal differentiation rates of newborn cells. Therefore, further studies on mechanisms regulating neurogenesis under ischemic conditions are required, among which ephrin-ligands and ephrin-receptors (Eph) are an interesting target. Although Eph/ephrin proteins like ephrin-B3 are known to negatively regulate neurogenesis under physiological conditions, their role in cerebral ischemia is largely unknown. We therefore studied neurogenesis, brain injury and functional outcome in ephrin-B3−/− (knockout) and ephrin-B3+/+ (wild-type) mice submitted to cerebral ischemia. Induction of stroke resulted in enhanced cell proliferation and neuronal differentiation around the lesion site of ephrin-B3−/− compared to ephrin-B3+/+ mice. However, prominent post-ischemic neurogenesis in ephrin-B3−/− mice was accompanied by significantly increased ischemic injury and motor coordination deficits that persisted up to 4 weeks. Ischemic injury in ephrin-B3−/− mice was associated with a caspase-3-dependent activation of the signal transducer and activator of transcription 1 (STAT1). Whereas inhibition of caspase-3 had no effect on brain injury in ephrin-B3+/+ animals, infarct size in ephrin-B3−/− mice was strongly reduced, suggesting that aggravated brain injury in these animals might involve a caspase-3-dependent activation of STAT1. In conclusion, post-ischemic neurogenesis in ephrin-B3−/− mice is strongly enhanced, but fails to contribute to functional recovery because of caspase-3-mediated aggravation of ischemic injury in these animals. Our results suggest that ephrin-B3 might be an interesting target for overcoming some of the limitations of further cell-based therapies in stroke

Lifetime study in mice after acute low-dose ionizing radiation: a multifactorial study with special focus on cataract risk

Because of the increasing application of ionizing radiation in medicine, quantitative data on effects of low-dose radiation are needed to optimize radiation protection, particularly with respect to cataract development. Using mice as mammalian animal model, we applied a single dose of 0, 0.063, 0.125 and 0.5 Gy at 10 weeks of age, determined lens opacities for up to 2 years and compared it with overall survival, cytogenetic alterations and cancer development. The highest dose was significantly associated with increased body weight and reduced survival rate. Chromosomal aberrations in bone marrow cells showed a dose-dependent increase 12 months after irradiation. Pathological screening indicated a dose-dependent risk for several types of tumors. Scheimpflug imaging of the lens revealed a significant dose-dependent effect of 1% of lens opacity. Comparison of different biological end points demonstrated long-term effects of low-dose irradiation for several biological end points

An experience-based value set for the EQ-5D-5L in Germany.

Objective: Valuation of health states provides a summary measure useful to health care decision makers. Results may depend on whether the currently experienced health state or a hypothetical health state is being evaluated. This study derives a value set for the EuroQoL Five-Dimensional Five-Level Questionnaire (EQ-5D-5L) by focusing on the individual&#39;s current experience. Data and Methods: Data include four pooled population surveys of the general German population in 2012-2015 (N = 8114). For valuation, a visual analogue scale (VAS) was used. Six specifications of a generalized linear model with binomial error distribution and constraint parameter estimation were analyzed. In each 1000 simulation runs, models were cross-validated after splitting the sample into an estimation part and a validation part. Predictive accuracy was measured by mean absolute error and sum of squared errors. Results: The models rendered a consistent set of parameters. With regard to predictive accuracy, the model considering all problem levels within the five dimensions and the highest problem level reached performed best overall. Discussion: Estimation proved to be feasible. Predictive accuracy exceeded that of a similar, experience-based value set for the EQ-5D-3L. Compared with a Dutch value set for the EQ-5D-5L derived for hypothetical health states, experienced values tended to be slightly lower for mild health states and substantially higher for severe health states. Clinical relevance and usefulness of the value set remain to be determined in future studies. Conclusions: For decision makers who prioritize patient-relevant benefit, the experience-based value set provides a novel option to summarize health states, reflecting how health states experienced are valued in a population

A value set for the EQ-5D based on experienced health states: Development and testing for the German population.

BACKGROUND: Decision makers responsible for allocation of healthcare resources may require that health states are valued by the population for whom they are making decisions. To achieve this, health-state descriptions can be combined with a value set that reflects the valuations of the target population. In the decision-utility approach, such a value set is at least partly based on wants and expectations regarding given health states. This may reflect aspects different from the health state experienced and valued by a respondent. OBJECTIVES: To derive a value set that is completely based on experienced health states, emphasising the patient&#39;s perspective, and test its predictive performance in comparison with established approaches. METHODS: Problem descriptions and rating scale valuations of the EQ-5D were drawn from two representative German population surveys in 2006 and 2007. Two models based on given health states but differing in valuation method (1a, b) were analysed, along with three models based on experienced health states: (2) ordinary least squares regression; (3) scale-transformed regression; and (4) a generalized linear model with binomial error distribution and constraint parameter estimation. The models were compared with respect to issues in specification, and accuracy in predicting the actual valuations of experienced health states in a new data set, using correlation, mean error and ranking measures for the latter. In addition, the impact of standardizing experience-based index models for age and sex of the subjects was investigated. RESULTS: Models 1 (a, b), 2 and 3 partly led to plausible and comparable parameter estimates, but also led to problems of insignificance and inconsistencies in some of the estimates. Model 4 achieved consistency and featured partly equivalent and partly better predictive accuracy. Using this model, mean valuations of health states were much better predicted by the experience-based approach than by the decision-utility approach, especially for health states that frequently (&gt;10) occurred in the population sample. Standardizing the experience-based index models for age and sex further improved predictive accuracy and strengthened the position of model 4. CONCLUSIONS: A value set for the EQ-5D can be plausibly estimated from experience-based valuations. The approach offers an alternative to decision makers who prefer experience-based valuation over decision utilities in the measurement of health outcome. Although usefulness in population samples was shown, use in a clinical context will first require indication-specific tests. Current limitations include use in a general population only, and a restricted range of health states covered

Exploration of energy metabolism in the mouse using indirect calorimetry: Measurement of Daily Energy Expenditure (DEE) and Basal Metabolic Rate (BMR).

Current comprehensive mouse metabolic phenotyping involves studying energy balance in cohorts of mice via indirect calorimetry, which determines heat release from changes in respiratory air composition. Here, we describe the measurement of daily energy expenditure (DEE) and basal metabolic rate (BMR) in mice. These well-defined metabolic descriptors serve as meaningful first-line read-outs for metabolic phenotyping and should be reported when exploring energy expenditure in mice. For further guidance, the issue of appropriate sample sizes and the frequency of sampling of metabolic measurements is also discussed