Strain difference in the effect of infralimbic cortex lesions on fear extinction in rats.

The infralimbic division of the medial prefrontal cortex (IL) has been implicated in the consolidation and retention of extinction memories. However, the effects of IL lesions on the retention of extinction memory are inconsistent. In the present experiments, we examined whether rat strain influences the effects of IL lesions on extinction. In Experiment 1, Sprague-Dawley (SD) or Long-Evans (LE) rats received a standard auditory fear conditioning procedure, which was followed by an extinction session; freezing served as the index of conditional fear. Our results reveal that focal IL lesions impair the retention of extinction in SD, but not LE rats. In addition to the strain difference in sensitivity to IL lesions, LE rats exhibited significantly higher levels of contextual fear before the outset of extinction training than SD rats. In a second experiment we thus examined whether contextual fear influenced the sensitivity of extinction to IL lesions in LE rats. LE rats received the same conditioning as in Experiment 1, and then were either merely exposed to a novel context or administered unsignaled shocks in that context, followed by extinction and test sessions. Our results reveal that LE rats with IL lesions showed normal extinction regardless of the levels of contextual fear manifest before extinction. Thus, we conclude that rat strain is an important variable that influences the role of infralimbic cortex in fear extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of acidosis in hypokalemic periodic paralysis

Metabolic acidosis was produced in two patients with hypokalemic periodic paralysis by the administration of ammonium chloride over a period of three days. The challenging test of glucose and insulin produced a substantially smaller reduction of both serum potassium concentration and muscle strength than when the patients were tested in normal acid-base balance. The findings agree with earlier work on acetazolamide, suggesting that metabolic acidosis provides protection against episodes of muscle weakness in periodic paralysis.     

Sorption of the veterinary antimicrobial sulfathiazole to organic materials of different origin

Sulfonamides (SA), ionizable, polar antimicrobial compounds, may reach the environment in substantial amounts by the spreading of manure. The environmental behavior of SA is still difficult to predict. We investigated the influence of the main factors supposed to control SA sorption to organic materials: composition of sorbent, solute chemistry, and contact time. For that purpose, sulfathiazole (STA) sorption to compost, manure, and humic acid after 1 and 14 d was studied under sterile conditions. The experiments demonstrated that sorption was most strongly affected by contact time and pH. Irrespective of sorbent and pH, sorption continued substantially after the fast initial sorption within 1 d. For all sorbents and both contact times, STA sorption exhibited a pronounced pH dependence. Species-specific Koc values decreased in the order KoccatiOn> Kocneutral > Kocanion. Differences in sorbent composition influenced STA sorption weaker. Forthe neutral STA species, NMR chemical shift regions assignable to ketonic, carboxylic, and phenolic C as well as aromatic C-H and methoxyl/N-alkyl C seemed to control sorption. Forthe cations, sorption followed the cation exchange capacities of the sorbents. STA sorption to manure and humic acid increased with higher ionic strength (0.31 M compared to 0.06 M) at pH 7.5.     

Long-Term Sex- and Genotype-Specific Effects of 56Fe Irradiation on Wild-Type and APPswe/PS1dE9 Transgenic Mice

Space radiation presents a substantial threat to travel beyond Earth. Relatively low doses of high-energy particle radiation cause physiological and behavioral impairments in rodents and may pose risks to human spaceflight. There is evidence that ⁵⁶Fe irradiation, a significant component of space radiation, may be more harmful to males than to females and worsen Alzheimer’s disease pathology in genetically vulnerable models. Yet, research on the long-term, sex- and genotype-specific effects of ⁵⁶Fe irradiation is lacking. Here, we irradiated 4-month-old male and female, wild-type and Alzheimer’s-like APP/PS1 mice with 0, 0.10, or 0.50 Gy of ⁵⁶Fe ions (1GeV/u). Mice underwent microPET scans before and 7.5 months after irradiation, a battery of behavioral tests at 11 months of age and were sacrificed for pathological and biochemical analyses at 12 months of age. ⁵⁶Fe irradiation worsened amyloid-beta (Aβ) pathology, gliosis, neuroinflammation and spatial memory, but improved motor coordination, in male transgenic mice and worsened fear memory in wild-type males. Although sham-irradiated female APP/PS1 mice had more cerebral Aβ and gliosis than sham-irradiated male transgenics, female mice of both genotypes were relatively spared from radiation effects 8 months later. These results provide evidence for sex-specific, long-term CNS effects of space radiation.     

Ringtransformationen heterocyclischer Verbindungen. XII. Neuartige Spiroindoline via Ringtransformation von 2,4,6-Triaryl-pyryliumsalzen mit 2-Methylen-indolinen

Ring Transformations of Heterocyclic Compounds. XII. Novel Spiroindolines via Ring Transformation of 2,4,6-Triarylpyrylium Salts with 2-Methyleneindolines 2,4,6-Triarylpyrylium salts 1 react with 2-methyleneindolines 2 or their salts 2 HX in the presence of triethylamine/acetic acid in ethanol by a 2,5-[C₄ + C₂] pyrylium ring transformation to give diastereomerically pure 6-aroyl-3,5-diaryl-spiro[cyclohexa-2,4-diene-1,2′-indolines] 3 , which represent a novel type of spiroindoline compounds. When the 1′-phenyl substituted spiroindolines 3 (RPh, R′H) are treated with p-toluenesulfonic acid in chloroform the 4,6-diaryl-2-[1-methyl-1-(2-phenylaminophenyl)methyl]benzophenones 4 are obtained as the result of an intramolecular amine elimination. Structural elucidation of the reaction products 3/4 is based on spectroscopic data and on an X-ray determination of the bis(4-bromophenyl) substituted spiroindoline 3i.     

Human Mesenchymal Stromal Cells Do Not Cause Radioprotection of Head-and-Neck Squamous Cell Carcinoma

Radiotherapy of head-and-neck squamous cell carcinoma (HNSCC) can cause considerable normal tissue injuries, and mesenchymal stromal cells (MSCs) have been shown to aid regeneration of irradiation-damaged normal tissues. However, utilization of MSC-based treatments for HNSCC patients undergoing radiotherapy is hampered by concerns regarding potential radioprotective effects. We therefore investigated the influence of MSCs on the radiosensitivity of HNSCCs. Several human papillomavirus (HPV)-negative and HPV-positive HNSCCs were co-cultured with human bone marrow-derived MSCs using two-dimensional and three-dimensional assays. Clonogenic survival, proliferation, and viability of HNSCCs after radiotherapy were assessed depending on MSC co-culture. Flow cytometry analyses were conducted to examine the influence of MSCs on irradiation-induced cell cycle distribution and apoptosis induction in HNSCCs. Immunofluorescence stainings of γH2AX were conducted to determine the levels of residual irradiation-induced DNA double-strand breaks. Levels of connective tissue growth factor (CTGF), a multifunctional pro-tumorigenic cytokine, were analyzed using enzyme-linked immunosorbent assays. Neither direct MSC co-culture nor MSC-conditioned medium exerted radioprotective effects on HNSCCs as determined by clonogenic survival, proliferation, and viability assays. Consistently, three-dimensional microwell arrays revealed no radioprotective effects of MSCs. Irradiation resulted in a G2/M arrest of HNSCCs at 96 h independently of MSC co-culture. HNSCCs’ apoptosis rates were increased by irradiation irrespective of MSCs. Numbers of residual γH2AX foci after irradiation with 2 or 8 Gy were comparable between mono- and co-cultures. MSC mono-cultures and HNSCC-MSC co-cultures exhibited comparable CTGF levels. We did not detect radioprotective effects of human MSCs on HNSCCs. Our results suggest that the usage of MSC-based therapies for radiotherapy-related toxicities in HNSCC patients may be safe in the context of absent radioprotection.     

Evaluation of UV-induced embrittlement of PE-HD by Charpy impact test

The impact fracture behavior of two common high-density polyethylene grades for container applications were intensively studied by the instrumented Charpy impact test after well-defined exposure to UV-irradiation. Individual stages of the impact event, such as crack initiation and crack propagation energy as well as maximum impact load, were investigated from the recorded load–deflection curves. UV-induced material property changes were further investigated by infrared spectroscopy, differential scanning calorimetry, and dynamic-mechanical analysis as well as density measurements. Based on the results of the Charpy impact test, three indicators were identified to describe the extend of photooxidation on high-density polyethylene: (a) a reduced Charpy impact strength—at least to half of its initial value for a distinctly brittle impact fracture, (b) a marked decrease in the crack propagation contribution to the impact strength, and (c) an increase of the brittle features of the fracture surface.     

Synthesis and Biological Evaluation of Nipecotic Acid and Guvacine Derived 1,3-Disubstituted Allenes as Inhibitors of Murine GABA Transporter mGAT1

A new class of nipecotic acid and guvacine derivatives has been synthesized and characterized for their inhibitory potency at mGAT1–4 and binding affinity for mGAT1. Compounds of the described class are defined by a four-carbon-atom allenyl spacer connecting the nitrogen atom of the nipecotic acid or guvacine head with an aromatic residue. Among the compounds investigated, the mixture of nipecotic acid derivatives rac-{(R_a)-1-[4-([1,1′:2′,1′′-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} and rac-{(S_a)-1-[4-([1,1′:2′,1′′-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} ( 21 p ), possessing an o-terphenyl residue, was identified as highly selective and the most potent mGAT1 inhibitor in this study. For the (R)-nipecotic acid derived form of 21 p , the inhibitory potency in [³H]GABA uptake assays was determined as pIC₅₀=6.78±0.08, and the binding affinity in MS Binding Assays as pK_i=7.10±0.12. The synthesis of the designed compounds was carried out by a two-step procedure, generating the allene moiety via allenylation of terminal alkynes which allows broad variation of the terminal phenyl and biphenyl subunit.