Frühmobilisation auf der Intensivstation – Sind robotergestützte Systeme die Zukunft?

Die Anaesthesiologie - Bei etwa 43?% aller Überlebenden der Intensivmedizin wird ein erworbenes Syndrom an Muskelschwäche beobachtet, welches Überleben und Lebensqualität...     

Effects of Intrathecally Administered Lamotrigine, a Glutamate Release Inhibitor, on Short- and Long-term Models of Hyperalgesia in Rats

Background: Lamotrigine is a sodium channel blocker that inhibits the neuronal release of glutamate. Systemic administration of lamotrigine induces analgesia in short- and long-term models of hyperalgesia in rats. Considering the key role of N-methyl-D-aspartate receptors in the sensitization of dorsal horn neurons that leads to hyperalgesia, the author hypothesizes that intrathecally injected lamotrigine would be effective in reducing the hyperalgesia.

Methods: Short-term hyperalgesia was induced by unilateral intraplantar injection of prostaglandin E2. Long-term hyperalgesia was produced by treating rats with streptozotocin, which causes diabetic neuropathy and, in a different group of animals, by loose ligation of the sciatic nerve (chronic constriction injury). Hyperalgesia was assessed by measuring withdrawal reaction time after paw pressure, and analgesia was measured by the thermal tail-flick test.

Results: In the short-term model, intrathecally administered lamotrigine (12.5, 25.0, and 100.0 micro gram) produced a dose-dependent increase in the reaction time of the hyperalgesic paw. The highest dose that completely restored the reaction time to control levels (26-29 s) from the hyperalgesic levels (12-15 s) did not affect the reaction time of the normal contralateral paw. In the tail-flick test, a consistent effect could be observed only with doses of 200 micro gram, which caused transient motor impairment of the hind paws. In the long-term models of hyperalgesia, intrathecally administered lamotrigine produced a dose-dependent and long-lasting (24-48 h) antihyperalgesic effect.     

Peripheral biomarkers and illness activity in bipolar disorder

Recent evidence suggests that peripheral markers related to oxidative stress, inflammation and neurotrophins may be altered during mood episodes in bipolar disorder. These can be seen as proxies of peripheral toxicity or markers of illness activity. Here we report an en bloc assessment of a set of previously described biomarkers in different mood states (n = 60) as well as in healthy subjects (n = 80). To make the point that these are ominous changes, we obtained the same measures from a group of septic patients (n = 15) as a “positive” control group. In this sample, we measured serum levels of brain derived neurotrophic factor, neurotrophin 3, tumor necrosis factor α, interleukin 6, interleukin 10, total reactive antioxidant potential, thiobarbituric acid reactive substances and protein carbonyl content. Several of the markers discriminated between the bipolar and control groups, especially when patients were in acute episodes. In some cases, toxicity was as high in bipolar disorder as that seen in patients with sepsis. We believe these findings highlight the potential of using biomarkers to assess illness activity in bipolar disorder.     

Validation of cofilin-1 as a biomarker in non-small cell lung cancer: application of quantitative method in a retrospective cohort

Purpose

Cofilin is a cytoskeletal protein whose overexpression has been associated with aggressiveness in several types of malignancies. Here, we established and optimized a simple semi-quantitative immunohistochemistry (SQ-IHC) method for cofilin quantification in tumor biopsies, and applied it in a retrospective cohort of NSCLC patients aiming at validating the use of cofilin-1 as a prognostic biomarker.

Methods

The SQ-IHC method for cofilin-1 quantification was established and applied in a NSCLC cohort. An archival collection of biopsies from 50 patients with clinicopathological information and 5?years follow-up was accessed. Association between cofilin-1 immunocontent and clinical outcome was assessed using standard Kaplan?CMeier mortality curves and the log-rank test. To evaluate the robustness of our findings, three different partitional clustering strategies were used to stratify patients into two groups according to the biomarker expression level (hierarchical clustering, Kmeans and median cutoff).

Results

In all the three different partitional clustering we used, survival analysis showed that patient with high cofilin-1 immunocontent had a lower overall survival rate (P?Conclusions Our method showed good sensitivity/specificity to indicate the outcome of patients according to their cofilin immunocontent in biological samples. Its application in a retrospective cohort and the results presented here are an important step toward the validation process of cofilin-1 as a prognostic biomarker.     

Evaluation of the Neurotoxic/Neuroprotective Role of Organoselenides Using Differentiated Human Neuroblastoma SH-SY5Y Cell Line Challenged with 6-Hydroxydopamine

It is well established that oxidative stress plays a major role in several neurodegenerative conditions, like Parkinson disease (PD). Hence, there is an enormous effort for the development of new antioxidants compounds with therapeutic potential for the management of PD, such as synthetic organoselenides molecules. In this study, we selected between nine different synthetic organoselenides the most eligible ones for further neuroprotection assays, using the differentiated human neuroblastoma SH-SY5Y cell line as in vitro model. Neuronal differentiation of exponentially growing human neuroblastoma SH-SY5Y cells was triggered by cultivating cells with DMEM/F12 medium with 1% of fetal bovine serum (FBS) with the combination of 10 μM retinoic acid for 7 days. Differentiated cells were further incubated with different concentrations of nine organoselenides (0.1, 0.3, 3, 10, and 30 μM) for 24 h and cell viability, neurites densities and the immunocontent of neuronal markers were evaluated. Peroxyl radical scavenging potential of each compound was determined with TRAP assay. Three organoselenides tested presented low cytotoxicity and high antioxidant properties. Pre-treatment of cells with those compounds for 24 h lead to a significantly neuroprotection against 6-hydroxydopamine (6-OHDA) toxicity, which were directly related to their antioxidant properties. Neuroprotective activity of all three organoselenides was compared to diphenyl diselenide (PhSe)?, the simplest of the diaryl diselenides tested. Our results demonstrate that differentiated human SH-SY5Y cells are suitable cellular model to evaluate neuroprotective/neurotoxic role of compounds, and support further evaluation of selected organoselenium molecules as potential pharmacological and therapeutic drugs in the treatment of PD.     

Elements of a general theory of joints. 6. General kinematical structure of mandibular movements.

Movements of the mandible are recorded in vivo by a measuring system (MT 1602) that takes all 6 degrees of freedom of a rigid body into account. Class-I-patients were asked to move their mandible in the sagittal-vertical plane. The evaluation of the measurements yields an almost plane mandibular movement that only uses 2 degrees of freedom although a general plane movement normally possesses 3 degrees and although the human temporomandibular joint (TMJ) has a certain space of motion. This quantitative reduction of the degrees of freedom by one is produced by a neuro-muscularly guided dimeric link chain that cannot directly be related to anatomical landmarks. The diverse types of mandibular motion of a sound patient differ in the constant ratio of the angular velocities around the 2 axes of the dimeric link chain. Therefore, the paths of the individual mandibular points are epicycloids or hypocycloids. Patients with disorders of the TMJ and the neuromuscular feedback system do no longer show this constancy of the angular velocities' ratio. Besides that, we theoretically derive and empirically prove the fact that common axiographs do not record the "path of the hinge axis" of the TMJ, on principle. In this context we discuss some--in dentistry and anatomy widespread--fundamental misconceptions of the rigid body's kinematics.