A combined DNA-microarray and mechanism-specific toxicity approach with zebrafish embryos to investigate the pollution of river sediments

The zebrafish embryo has repeatedly proved to be a useful model for the analysis of effects by environmental toxicants. This proof-of-concept study was performed to investigate if an approach combining mechanism-specific bioassays with microarray techniques can obtain more in-depth insights into the ecotoxicity of complex pollutant mixtures as present, e.g., in sediment extracts. For this end, altered gene expression was compared to data from established bioassays as well as to results from chemical analysis. Mechanism-specific biotests indicated a defined hazard potential of the sediment extracts, and microarray analysis revealed several classes of significantly regulated genes which could be related to the hazard potential. Results indicate that potential classes of contaminants can be assigned to sediment extracts by both classical biomarker genes and corresponding expression profile analyses of known substances. However, it is difficult to distinguish between specific responses and more universal detoxification of the organism.     

Differential host determinants contribute to the pathogenesis of 2009 pandemic H1N1 and human H5N1 influenza A viruses in experimental mouse models

Influenza viruses are responsible for high morbidities in humans and may, eventually, cause pandemics. Herein, we compared the pathogenesis and host innate immune responses of a seasonal H1N1, two 2009 pandemic H1N1, and a human H5N1 influenza virus in experimental BALB/c and C57BL/6J mouse models. We found that both 2009 pandemic H1N1 isolates studied (A/Hamburg/05/09 and A/Hamburg/NY1580/09) were low pathogenic in BALB/c mice [log mouse lethal dose 50 (MLD(50)) >6 plaque-forming units (PFU)] but displayed remarkable differences in virulence in C57BL/6J mice. A/Hamburg/NY1580/09 was more virulent (logMLD(50) = 3.5 PFU) than A/Hamburg/05/09 (logMLD(50) = 5.2 PFU) in C57BL/6J mice. In contrast, the H5N1 influenza virus was more virulent in BALB/c mice (logMLD(50) = 0.3 PFU) than in C57BL/6J mice (logMLD(50) = 1.8 PFU). Seasonal H1N1 influenza revealed marginal pathogenicity in BALB/c or C57BL/6J mice (logMLD(50) >6 PFU). Enhanced susceptibility of C57BL/6J mice to pandemic H1N1 correlated with a depressed cytokine response. In contrast, enhanced H5N1 virulence in BALB/c mice correlated with an elevated proinflammatory cytokine response. These findings highlight that host determinants responsible for the pathogenesis of 2009 pandemic H1N1 influenza viruses are different from those contributing to H5N1 pathogenesis. Our results show, for the first time to our knowledge, that the C57BL/6J mouse strain is more appropriate for the evaluation and identification of intrinsic pathogenicity markers of 2009 pandemic H1N1 influenza viruses that are "masked" in BALB/c mice.     

Triggering for Submaximal Exercise Level in Gastric Exercise Tonometry: Serial Lactate,Heart Rate,or Respiratory Quotient?

Gastric exercise tonometry is a functional diagnostic test in chronic gastrointestinal ischemia. As maximal exercise can cause false-positive tests, exercise buildup should be controlled to remain submaximal. We evaluated three parameters for monitoring and adjusting exercise levels (heart rate [HR], respiratory quotient [RQ], and serial lactate measurements) in 178 tests in both healthy volunteers and patients suspected of gastrointestinal ischemia. Exercise levels above submaximal occurred in 20% of HR-, 2% of RQ-, and 5% of lactate-monitored tests (P<0.05 for HR vs. RQ and lactate). Low levels were seen in 5% of HR-, 10% of RQ-, and 41% of lactate-monitored tests (P<0.01 for lactate vs. HR and RQ). High levels resulted in 43% false-positive tonometry results compared to 19% of all tests (P<0.001); low levels did not result in more false negatives (5% vs. 6%). Although RQ monitoring yielded the greatest proportion of optimal exercise tests, serial lactate monitoring is our method of choice, combining optimal diagnostic accuracy, low cost, and simplicity.     

Drug development parameters for functional imaging in neurosciences

State-of-the-art radioactive drug development has become a helpful tool in new functional imaging technologies in neurosciences. Drug development programs are evaluated in terms of effective biodistribution, costs and time. This article details the existing drug development parameters for neuroimaging and highlights some examples, as in Parkinson's disease, alcoholic neuritis and psychotic diseases, showing the benefit and the potential of using new functional neuroimaging technologies for specific studies of the central nervous system.     

Blood Markers of Inflammation,Neurodegeneration, and Cardiovascular Risk in Early Parkinson's Disease

Background

Recent studies point toward a significant impact of cardiovascular processes and inflammation on Parkinson's disease (PD) progression.

Objective

The aim of this study was to assess established markers of neuronal function, inflammation, and cardiovascular risk by high-throughput sandwich immune multiplex panels in deeply phenotyped PD.

Methods

Proximity Extension Assay technology on 273 markers was applied in plasma of 109 drug-naive at baseline (BL) patients with PD (BL, 2-, 4-, and 6-year follow-up [FU]) and 96 healthy control patients (HCs; 2- and 4-year FU) from the de novo Parkinson's cohort. BL plasma from 74 individuals (37 patients with PD, 37 healthy control patients) on the same platform from the Parkinson Progression Marker Initiative was used for independent validation. Correlation analysis of the identified markers and 6 years of clinical FU, including motor and cognitive progression, was evaluated.

Results

At BL, 35 plasma markers were differentially expressed in PD, showing downregulation of atherosclerotic risk markers, eg, E-selectin and ß₂-integrin. In contrast, we found a reduction of markers of the plasminogen activation system, eg, urokinase plasminogen activator. Neurospecific markers indicated increased levels of peripheral proteins of neurodegeneration and inflammation, such as fibroblast growth factor 21 and peptidase inhibitor 3. Several markers, including interleukin-6 and cystatin B, correlated with cognitive decline and progression of motor symptoms during FU. These findings were independently validated in the Parkinson Progression Marker Initiative.

Conclusions

We identified and validated possible PD plasma biomarker candidates for state, fate, and disease progression, elucidating new molecular processes with reduced endothelial/atherosclerotic processes, increased thromboembolic risk, and neuroinflammation. Further investigations and validation in independent and larger longitudinal cohorts are needed. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Severe thoracic trauma: under what accident and resuscitation conditions can it still be treated?

Severe thoracic trauma is a major cause of early death following road accident. 569 non-surviving and 112 surviving victims of traffic casualties were documented by the Accident Research Unit of the Clinic of Trauma Surgery, Hannover Medical School from 1973 to 1987. Medical data and measures of rescue were evaluated with a view to way of clinical therapies, lethal outcome and time of death. Primary intubation and chest draining seems to be the most successful initial treatment on the scene and during transport.     

Operative treatment in case of a closed rupture of the anterior tibial tendon

Closed rupture of the tibial anterior tendon is a rare clinical entity. Case reports in the literature reveal a total of only 49 cases up to the year 2000. According to these reports, the age group affected is 50 to 70 years old, and there are more men than women affected. Although the functional limitation is quite considerable, late diagnosis is common. An appropriate clinical examination, including an exact history taking, should lead to the right diagnosis. Ultrasound examination and magnetic resonance imaging (MRI) may be helpful. 'Restitutio ad integrum' can only be achieved by operative treatment. If technically possible, reinsertion of the tendon directly into bone or direct tendon repair is preferred. After delayed diagnosis, a secondary reconstruction through tendon transfer or transplantation is often necessary. A 64-year-old woman presented with pain and swelling in the area of the ankle joint 5 months after falling. She showed insecurity in walking, and the heel-walk could not be demonstrated. The distal neurovascular function was intact. The area of the retinaculum showed a swelling, and the tendon was not palpable in comparison with the other forefoot. An intact tendon could not be seen by ultrasound, and MRI confirmed these findings. A complete rupture was noted during the operative revision. The proximal and the distal tendon stumps were found to be thickened and knotted, the proximal stump was also atrophic. An augmented tenoplasty was performed. Afterwards, the tendon was tense in the neutral position. The lower leg was put in a plaster cast for 6 weeks, followed by physiotherapy. Ten months after the operation, the tendon was palpable in the correct position, the dorsal extension was powerful, and the patient did not experience any difficulty. Rupture of the anterior tibial tendon is a rare clinical entity and should be considered in the differential diagnosis of pain in the area of the ankle joint. An early operative treatment is advantageous.