Compaction properties of isomalt

Although other polyols have been described extensively as filler-binders in direct compaction of tablets, the polyol isomalt is rather unknown as pharmaceutical excipient, in spite of its description in all the main pharmacopoeias. In this paper the compaction properties of different types of ispomalt were studied. The types used were the standard product sieved isomalt, milled isomalt and two types of agglomerated isomalt with a different ratio between 6-O-alpha-D-glucopyranosyl-D-sorbitol (GPS) and 1-O-alpha-D-glucopyranosyl-D-mannitol dihydrate (GPM). Powder flow properties, specific Surface area and densities of the different types were investigated. Compactibility was investigated by compression of the tablets on a compaction Simulator, simulating the compression oil high-speed tabletting machines. Lubricant sensitivity was measured by compressing unlubricated tablets and tablets lubricated with 1% magnesium stearate oil all instrumented hydraulic press. Sieved isomair had excellent flow properties but the compactibility was found to be poor whereas the lubricant sensitivity was high. Milling resulted in both a strong increase in compactibility as an effect of the higher surface area for bonding and a decrease in lubricant sensitivity as an effect of the higher Surface area to be coated with magnesium stearate. However, the flow properties of milled isomalt were too bad for use as filler-binder in direct compaction. just as could be expected, agglomeration of milled isomalt by fluid bed agglomeration improved flowability. The good compaction properties and the low lubricant sensitivity were maintained. This effect is Caused by all early fragmentation of the agglomerated material during the compaction process, producing clean, lubricant-free particles and a high Surface for bonding. The different GPS/GPM ratios of the agglomerated isomalt types Studied had no significant effect oil the compaction properties. (C) 2009 Elsevier B.V. All rights reserved

Exploring mechanisms of compaction in salt-marsh sediments using Common Era relative sea-level reconstructions

Salt-marsh sediments provide precise and near-continuous reconstructions of Common Era relative sea level (RSL). However, organic and low-density salt-marsh sediments are prone to compaction processes that cause post-depositional distortion of the stratigraphic column used to reconstruct RSL. We compared two RSL reconstructions from East River Marsh (Connecticut, USA) to assess the contribution of mechanical compression and biodegradation to compaction of salt-marsh sediments and their subsequent influence on RSL reconstructions. The first, existing reconstruction (‘trench’) was produced from a continuous sequence of basal salt-marsh sediment and is unaffected by compaction. The second, new reconstruction is from a compaction-susceptible core taken at the same location. We highlight that sediment compaction is the only feasible mechanism for explaining the observed differences in RSL reconstructed from the trench and core. Both reconstructions display long-term RSL rise of ∼1 mm/yr, followed by a ∼19th Century acceleration to ∼3 mm/yr. A statistically-significant difference between the records at ∼1100 to 1800 CE could not be explained by a compression-only geotechnical model. We suggest that the warmer and drier conditions of the Medieval Climate Anomaly (MCA) resulted in an increase in sediment compressibility during this time period. We adapted the geotechnical model by reducing the compressive strength of MCA sediments to simulate this softening of sediments. ‘Decompaction’ of the core reconstruction with this modified model accounted for the difference between the two RSL reconstructions. Our results demonstrate that compression-only geotechnical models may be inadequate for estimating compaction and post-depositional lowering of susceptible organic salt-marsh sediments in some settings. This has important implications for our understanding of the drivers of sea-level change. Further, our results suggest that future climate changes may make salt marshes more susceptible to the impacts of RSL rise by enhancing sediment compressibility. We stress, however, that the cause of the softening remains enigmatic. Until this is better constrained, it is premature to widely extrapolate our findings to existing core-based reconstructions of Holocene RSL

The involvement of aβ in the neuroinflammatory response

In the same year as Alzheimer described the case of Auguste D. as a peculiar disease of the cerebral cortex, Fischer published his classic paper about miliary plaque formation in a large number of brains from patients with senile dementia [1]. In this paper and a following one from 1910, Fischer stated that plaque formation is the result of the deposition of a peculiar foreign substance in the cortex that induces a regenerative response of the surrounding nerve fibers [2]. He described spindle-shaped thickening of nerve fibers terminating with club forms in the corona of plaques (Fig. 4.1). These altered nerve fibers were considered as axonal sprouting, and the terminal club forms showed a strong similarity with the clubshaped buddings of axons found in developing nerve fibers and after transections of peripheral nerves as described by Cajal some years earlier. According to Fischer, the crucial step of the plaque formation is the deposition of a foreign substance that provokes a local inflammatory response step followed by a regenerative response of the surrounding nerve fibers. However, Fischer could not find morphological characteristics of an inflammatory process around the plaques after extensive histopathological observations including complement binding studies. The only tissue reaction appeared to be an overgrowth of club-formed neurites

Can lifestyle modification improve neurocognition? Rationale and design of the ENLIGHTEN clinical trial

BACKGROUND: Risk factors for cardiovascular disease (CVD) not only increase the risk for clinical CVD events, but also are associated with a cascade of neurophysiologic and neuroanatomic changes that increase the risk of cognitive impairment and dementia. Although epidemiological studies have shown that exercise and diet are associated with lower CVD risk and reduced incidence of dementia, no randomized controlled trial (RCT) has examined the independent effects of exercise and diet on neurocognitive function among individuals at risk for dementia. The ENLIGHTEN trial is a RCT of patients with CVD risk factors who also are characterized by subjective cognitive complaints and objective evidence of neurocognitive impairment without dementia (CIND) STUDY DESIGN: A 2 by 2 design will examine the independent and combined effects of diet and exercise on neurocognition. 160 participants diagnosed with CIND will be randomly assigned to 6 months of aerobic exercise, the DASH diet, or a combination of both exercise and diet; a (control) group will receive health education but otherwise will maintain their usual dietary and activity habits. Participants will complete comprehensive assessments of neurocognitive functioning along with biomarkers of CVD risk including measures of blood pressure, glucose, endothelial function, and arterial stiffness. CONCLUSION: The ENLIGHTEN trial will (a) evaluate the effectiveness of aerobic exercise and the DASH diet in improving neurocognitive functioning in CIND patients with CVD risk factors; (b) examine possible mechanisms by which exercise and diet improve neurocognition; and (c) consider potential moderators of treatment, including subclinical CVD