Modulation des oxidativen Stresses in der humanen Altershaut

Zusammenfassung Oxidativer Stre? (UV-Licht, freie Radikale) ist einer der wesentlichen Ausl?ser für vorzeitige Hautalterung. Als aktive Schutzmechanismen gegen diese oxidativen Sch?den, die besonders im Alter zunehmen, k?nnen Koenzym Q10 (CoQ10), aber auch exogen applizierte Antioxidanzien wirken. Unsere vergleichenden In-vitro- und In-vivo-Untersuchungen an Haut alter Probanden zeigen anhand der Me?parameter (ultraschwache Photonenemission, Gesamtthiolstatus, Mitochondrienmembranpotential und Zellvitalit?t), da? die endogene Resistenz gegen UV-Licht in Keratinozyten alter Spender reduziert ist. Diese geringere Resistenz, d.h. der schlechtere Schutz der epidermalen Zellen gegen oxidative Stressoren, insbesondere gegen UV-Licht, kann durch topische Applikation von Verbindungen wie CoQ10 und Antioxidanzien wie alpha-Glucosylrutin (15) deutlich verbessert werden. Placebokontrollierte In-vivo-Studien zeigen au?erdem, da? bereits vorhandene, vornehmlich durch Lichtalterung (Photoaging) bedingte Hautver?nderungen, wie z.B. sichtbare F?ltchen im Bereich der Augenwinkel, durch topische Langzeitbehandlung mit humanidentischem CoQ10 deutlich reduziert werden k?nnen. Eingegangen: 5. August 1998, Akzeptiert: 25. Januar 1999     

A pilot study of daily subcutaneous interleukin-10 in patients with chronic hepatitis C infection.

The Th1/Th2 cytokine balance is important in persistence of infection and liver injury in chronic hepatitis C. The aim of this study was to administer the anti-inflammatory cytokine, recombinant human interleukin-10 (rHuIL-10), for 28 days in patients with chronic hepatitis C and to assess the safety and measure the effect on alanine aminotransferase (ALT, a marker of hepatic inflammation) levels and serum hepatitis C virus (HCV) RNA values. Three treatment-naive and 13 interferon (IFN) nonresponder patients (total 16 patients) with compensated chronic HCV infection were enrolled in this study. Patients were randomized to receive rHuIL-10 at a dose of 4 or 8 microg/kg/day as a single daily subcutaneous injection for 28 days. ALT values and serum HCV RNA were measured at days 0, 1, 3, 8, 15, 22, and 28 during therapy and at follow-up 2 and 4 weeks after cessation of the 4-week treatment period. ALT values normalized in 9 of 16 patients during therapy and remained normal until the end of treatment in 8 patients. The decreases in ALT values occurred in both the 4 microg and 8 microg dosage groups and were seen in both IFN naive and nonresponder patients. Mean ALT values fell significantly during the study period but usually returned to pretreatment levels by the end of the 4-week follow-up period (p < 0.05). HCV RNA concentrations did not vary significantly during or after therapy. (No patient had either an increase or a decrease in HCV RNA levels of > or =1.5 log during the study.) The drug was well tolerated, with no adverse symptoms noted. Platelet counts fell transiently to 73,000 and 63,000 in 2 patients. No other toxicity was observed, and no patients discontinued therapy. In chronic hepatitis C, short-term therapy with IL-10 was well tolerated and caused transient normalization of ALT values in 50% of patients, which returned to pretreatment levels on cessation of treatment. There were no significant changes observed in serum HCV RNA concentrations during the study. These immunomodulatory effects are similar to those observed with ribavirin monotherapy in chronic hepatitis C. Further study of rHuIL-10 alone or in combination with antiviral agents in chronic hepatitis C is warranted.     

A stereotaxic atlas of the forebrain of the bank vole (Clethrionomys glareolus)

In this article part of the forebrain of the bank vole (Clethrionomys glareolus) is presented in stereotaxic coordinates. The stereotaxic procedure was performed as follows. With the vole’s head mounted in a stereotaxic adaptor, internal reference tracks were made with a 0.5-mm diameter microdialysis cannula and India ink, 2 mm in front and 2.6 mm behind the skull landmark bregma. Brains were fixed for 72 h in 4% commercial formaldehyde in sodiumcacodylate buffer containing 1% CaCl₂. To determine shrinkage they were weighed before and after fixation. After embedding in paraffin they were sectioned at 25 μm and stained with Nissl. Photomicrographs were taken from the brain of one animal while its frontal (antero-posterior) coordinates of five neural structures were compared with those of 12 other voles. Variability was also checked in lateral and vertical directions at frontal level −1.0 mm (relative to bregma). The results show that the distance between the two skull landmarks bregma and lambda correlates significantly and negatively with the antero-posterior position of each of the brain areas. On the basis of these results an equation is proposed to improve accuracy in locating neural structures that deviate due to biological variability.     

Motor Cortex Causally Contributes to Vocabulary Translation following Sensorimotor-Enriched Training

The role of the motor cortex in perceptual and cognitive functions is highly controversial. Here, we investigated the hypothesis that the motor cortex can be instrumental for translating foreign language vocabulary. Human participants of both sexes were trained on foreign language (L2) words and their native language translations over 4 consecutive days. L2 words were accompanied by complementary gestures (sensorimotor enrichment) or pictures (sensory enrichment). Following training, participants translated the auditorily presented L2 words that they had learned. During translation, repetitive transcranial magnetic stimulation was applied bilaterally to a site within the primary motor cortex (Brodmann area 4) located in the vicinity of the arm functional compartment. Responses within the stimulated motor region have previously been found to correlate with behavioral benefits of sensorimotor-enriched L2 vocabulary learning. Compared to sham stimulation, effective perturbation by repetitive transcranial magnetic stimulation slowed down the translation of sensorimotor-enriched L2 words, but not sensory-enriched L2 words. This finding suggests that sensorimotor-enriched training induced changes in L2 representations within the motor cortex, which in turn facilitated the translation of L2 words. The motor cortex may play a causal role in precipitating sensorimotor-based learning benefits, and may directly aid in remembering the native language translations of foreign language words following sensorimotor-enriched training. These findings support multisensory theories of learning while challenging reactivation-based theories.SIGNIFICANCE STATEMENT Despite the potential for sensorimotor enrichment to serve as a powerful tool for learning in many domains, its underlying brain mechanisms remain largely unexplored. Using transcranial magnetic stimulation and a foreign language (L2) learning paradigm, we found that sensorimotor-enriched training can induce changes in L2 representations within the motor cortex, which in turn causally facilitate the translation of L2 words. The translation of recently acquired L2 words may therefore rely not only on auditory information stored in memory or on modality-independent L2 representations, but also on the sensorimotor context in which the words have been experienced.     

Somatic isoform of angiotensin I–converting enzyme in the pathology of testicular germ cell tumors

Retained fetal expression of angiotensin I–converting enzyme (ACE, CD143) has recently been shown in intratubular germ cell neoplasms (IGCN) and invasive germ cell tumors (GCT), suggesting the somatic isoform (sACE) as a characteristic component of neoplastic germ cells. We analyzed the distribution of sACE in 159 testicular GCT, including 87 IGCN. sACE protein was determined by immunohistochemistry (MAb CG2) on routinely formalin-fixed and paraffin-embedded tissue sections, supplemented by mRNA expression analysis using in situ hybridization. These data were compared with those obtained by germ cell/placental alkaline phosphatases (PIAP; MAbs PL8-F6 and 8A9) employing an uniform score system for the evaluation of immunoreactivity (IRS; possible values from 0 to 12). Expression of sACE and PIAP was found in all 87 analyzed IGCN (IRS > 4, median IRS of 12). Heterogeneous staining patterns were not related to the type of adjacent GCT but correlated with low expression in adjacent seminomas (P = .032 for sACE; P = .005 for PIAP). Both sACE and PIAP often showed a decreased and more heterogeneous but still moderate expression in 91 classic seminomas (median IRS of 8) and were completely absent in tumor cells of spermatocytic seminomas. Despite all similarities, we found sACE and PIAP differently regulated during GCT progression. This was documented by a well-preserved expression of either sACE or PIAP or both in all classic seminomas, low PIAP immunoreactivity in metastasis of seminomas, and completely diverging expression patterns in nonseminomatous GCT. Our findings underline the close molecular relationship between IGCN and seminoma, and suggest sACE as an appropriate marker for seminomatous differentiated tumors. H P 31:1466-1476.     

Intrinsic neural network dynamics in catatonia

Catatonia is a transnosologic psychomotor syndrome with high prevalence in schizophrenia spectrum disorders (SSD). There is mounting neuroimaging evidence that catatonia is associated with aberrant frontoparietal, thalamic and cerebellar regions. Large‐scale brain network dynamics in catatonia have not been investigated so far. In this study, resting‐state fMRI data from 58 right‐handed SSD patients were considered. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). Group spatial independent component analysis was carried out with a multiple analysis of covariance (MANCOVA) approach to estimate and test the underlying intrinsic components (ICs) in SSD patients with (NCRS total score ≥ 3; n = 30) and without (NCRS total score = 0; n = 28) catatonia. Functional network connectivity (FNC) during rest was calculated between pairs of ICs and transient changes in connectivity were estimated using sliding windowing and clustering (to capture both static and dynamic FNC). Catatonic patients showed increased static FNC in cerebellar networks along with decreased low frequency oscillations in basal ganglia (BG) networks. Catatonic patients had reduced state changes and dwelled more in a state characterized by high within‐network correlation of the sensorimotor, visual, and default‐mode network with respect to noncatatonic patients. Finally, in catatonic patients according to DSM‐IV‐TR (n = 44), there was a significant correlation between increased within FNC in cortico‐striatal state and NCRS motor scores. The data support a neuromechanistic model of catatonia that emphasizes a key role of disrupted sensorimotor network control during distinct functional states.