Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems

Rodent models of focal cerebral ischemia are essential tools in experimental stroke research. They have added tremendously to our understanding of injury mechanisms in stroke and have helped to identify potential therapeutic targets. A plethora of substances, however, in particular an overwhelming number of putative neuroprotective agents, have been shown to be effective in preclinical stroke research, but have failed in clinical trials. A lot of factors may have contributed to this failure of translation from bench to bedside. Often, deficits in the quality of experimental stroke research seem to be involved. In this article, we review the commonest rodent models of focal cerebral ischemia - middle cerebral artery occlusion, photothrombosis, and embolic stroke models - with their respective advantages and problems, and we address the issue of quality in preclinical stroke modeling as well as potential reasons for translational failure

Inhibition of Bacterial Adherence on the Surface of Stents and Bacterial Growth in Bile by Bismuth Dimercaprol

Bacterial infection and biofilm formation on the surface of biliary stents is believed to be one of the main factors in stent occlusion. This study explored the role of the new reagent, bismuth dimercaprol, in preventing bacterial adherence and bacterial biofilm formation on the surface of biliary stents. Sterile porcine bile preparations, infected separately with Escherichia coli, Klebsiella pneumoniae, Enterobacter , and Enterococcus , were used as the perfusion media in an in vitro perfusion system. The bacterial growth in the media and the bacterial adherence on the surface of stents were tested when different concentrations of bismuth dimercaprol were used in the perfusion media. BisBAL (5 μ M ) did not inhibit the growth of any of the tested bacterial species. It did, however, significantly decrease the amount of bacteria adhering to the surface of stents for all bacterial strains except Escherichia coli . Bismuth dimercaprol (20 μ M ) significantly inhibited the growth of Escherichia coli, Klebsiella pneumoniae , and Enterobacter and, thereby, significantly decreased the amount of these bacteria adhering to the surface of stents. The unique bactericidal and anitbiofilm activities of bismuth thiols might contribute to delaying the process of biliary stent occlusion if the effective concentrations of bismuth thiols could be delivered to the target sites. The feasibility of this application of bismuth thiols deserves further investigation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44439/1/10620_2005_Article_2702.pd

Response of cell wall composition and RNA-seq transcriptome to methyl-jasmonate in Brachypodium distachyon callus

Main conclusion: Methyl-jasmonate induces large increases in p-coumarate linked to arabinoxylan in Brachypodium and in abundance of GT61 and BAHD family transcripts consistent with a role in synthesis of this linkage. Jasmonic acid (JA) signalling is required for many stress responses in plants, inducing large changes in the transcriptome, including up-regulation of transcripts associated with lignification. However, less is known about the response to JA of grass cell walls and the monocot-specific features of arabinoxylan (AX) synthesis and acylation by ferulic acid (FA) and para-coumaric acid (pCA). Here, we show that methyl-jasmonate (MeJA) induces moderate increases in FA monomer, > 50% increases in FA dimers, and five–sixfold increases in pCA ester-linked to cell walls in Brachypodium callus. Direct measurement of arabinose acylated by pCA (Araf-pCA) indicated that most or all the increase in cell-wall pCA was due to pCA ester-linked to AX. Analysis of the RNA-seq transcriptome of the callus response showed that these cell-wall changes were accompanied by up-regulation of members of the GT61 and BAHD gene families implicated in AX decoration and acylation; two BAHD paralogues were among the most up-regulated cell-wall genes (seven and fivefold) after 24 h exposure to MeJA. Similar responses to JA of orthologous BAHD and GT61 transcripts are present in the RiceXPro public expression data set for rice seedlings, showing that they are not specific to Brachypodium or to callus. The large response of AX-pCA to MeJA may, therefore, indicate an important role for this linkage in response of primary cell walls of grasses to JA signalling

Laboratory review: the role of gait analysis in seniors' mobility and fall prevention

Walking is a complex motor task generally performed automatically by healthy adults. Yet, by the elderly, walking is often no longer performed automatically. Older adults require more attention for motor control while walking than younger adults. Falls, often with serious consequences, can be the result. Gait impairments are one of the biggest risk factors for falls. Several studies have identified changes in certain gait parameters as independent predictors of fall risk. Such gait changes are often too discrete to be detected by clinical observation alone. At the Basel Mobility Center, we employ the GAITRite electronic walkway system for spatial-temporal gait analysis. Although we have a large range of indications for gait analyses and several areas of clinical research, our focus is on the association between gait and cognition. Gait analysis with walking as a single-task condition alone is often insufficient to reveal underlying gait disorders present during normal, everyday activities. We use a dual-task paradigm, walking while simultaneously performing a second cognitive task, to assess the effects of divided attention on motor performance and gait control. Objective quantification of such clinically relevant gait changes is necessary to determine fall risk. Early detection of gait disorders and fall risk permits early intervention and, in the best-case scenario, fall prevention. We and others have shown that rhythmic movement training such as Jaques-Dalcroze eurhythmics, tai chi and social dancing can improve gait regularity and automaticity, thus increasing gait safety and reducing fall risk

Morphometric and immunohistochemical study of the omasum of red deer during prenatal development

The red deer is an important study species because of its value in the national economy and because it provides a wealth of genetic material. To date, there has been little research into the prenatal development of the stomach of ruminants, and none of the red deer. We therefore performed a histological evaluation of the ontogenesis of the omasum in the red deer. Histomorphometric and immunohistochemical analyses were carried out on 50 embryos and fetuses of deer from the initial stages of prenatal life until birth. For test purposes, the animals were divided into five experimental groups: Group I (1.4–3.6 cm crown–rump length, CRL; 30–60 days, 1–25% of gestation); Group II (4.5–7.2 cm CRL; 67–90 days, 25–35% of gestation); Group III (8–19 cm CRL; 97–135 days, 35–50% of gestation); Group IV (21–33 cm CRL; 142–191 days, 50–70% of gestation); and Group V (36–40 cm CRL; 205–235 days, 75–100% of gestation). At 67 embryonic days, the omasum wall was differentiated, and comprised three layers: the epithelial layer, pluripotential blastemic tissue and serosa. The stratification of the epithelial layer was accompanied by changes in its structure, with the appearance of four laminae of different sizes; in order of appearance these were: primary at 67 days, secondary at 90 days, tertiary at 97 days and quaternary at 135 days. At around mid-gestation, lateral evaginations were formed from the stratum basale of the primary and secondary smaller laminae. These were the primitive corneum papillae. From 205 days, the corneum papillae were present in all four sizes of laminae. The histodifferentiation of the lamina propia-submucosa, tunica muscularis and serosa showed patterns of development similar to those reported for the rumen and reticulum of red deer. The omasum of red deer during prenatal life, especially from 67 days of gestation, was shown to be an active structure with full secretory capacity. Its histological development, its secretory capacity (detected by the presence of neutral mucopolysaccharides) and its neuroendocrine nature (detected by the presence of positive non-neuronal enolase cells and the neuropeptides vasoactive intestinal peptide and neuropeptide Y) were parallel to the development of the rumen and the reticulum. However, its prenatal development was later than that of the omasum in sheep, goat and cow