Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.     

Intra- and inter-laboratory reproducibility of estrogen and progesterone receptor enzyme immunoassay in breast cancer cytosol samples--a Swedish multicenter study. Swedish Society of Cancer Study Group

Estrogen and progesterone receptor analysis results were compared within and between six laboratories in Sweden using frozen breast cancer cytosol samples, and the same technique (enzyme immunoassay, Abbott Laboratories). The concordance in receptor status (positive vs. negative) was excellent (98.4% (571/580)). The discordant results were attributable to values near cut-off (n = 4) or outliers (n = 5), the latter probably being due to analytical errors. One laboratory reported significantly higher ER concentrations than the others; thus caution should be observed when comparing absolute values from different centers. For PgR there were similar differences between the laboratories. However, the intra- and inter-laboratory differences were small compared with the overall variability in ER and PgR content between different samples in a large database. The range of the median intra-laboratory coefficient of variation was 11-23% for ER and 12-19% for PgR, indicating that there is room for improvement in the quality of assay performance.     

Effects of citrate on the different phases of calcium oxalate crystallization

Urinary citrate appears to be an important factor in the crystallization process of calcium oxalate and calcium phosphate. The urinary excretion of citrate was found to be significantly lower in patients with calcium oxalate stone disease as compared with normal subjects, and about 30 per cent of the calcium stone formers can be considered as hypocitraturic. The lowest excretion of citrate was recorded in urine collected during the night. Citrate has significant effects on supersaturation with respect to both calcium oxalate and calcium phosphate, it also inhibits the growth of these crystals. In addition, citrate appears to be capable of inhibiting the aggregation of crystals composed of calcium oxalate, brushite, and hydroxyapatite. The heterogenous growth of calcium oxalate on calcium phosphate is also counteracted by citrate. As a consequence of the crucial role of citrate in these processes, stone prevention with alkaline citrate has become an attractive form of treatment in patients with recurrent stone formation. Single evening dose administration of sodium potassium citrate resulted in an of sodium potassium citrate resulted in an increased excretion of citrate, reduced levels of the calcium/citrate ratio as well as supersaturation with respect to calcium oxalate and a decreased rate of stone formation. However, conflicting results of stone preventive treatment with alkaline citrate have been reported by different groups, and long-term follow-up of patients treated in a randomized way is necessary to definitely assess the efficacy of alkaline citrate.     

Investigations of delamination criticality and the transferability of growth criteria

This article describes a study of delamination growth along 0 °/0 °, 0 °/ 5 °, ± 5 °, and 0 °/90 ° interfaces sandwiched between unidirectional carbon fibre/epoxy composite material. Relationships between damage criticality, growth rate and acoustic emission activity for delamination growth have been studied and the transferability of results from laboratory coupons to composite structural elements has been examined. Two types of coupon tests, conventional delamination beams and rigidly loaded single edge notched strips, have been compared for different mode ratios. Comparative tests have been made on buckling-induced delamination in plates. A graphite crack gauge has been used to measure delamination length and growth rate, ranging from 0.05–2000 m/s. Damage growth was also followed using visual, ultrasonic C-scan, X-ray radiography, macro-video and acoustic emission measurements. Empirical evaluations of interlaminar toughness for delamination beams are made using the Irwin-Kies relation. Unstable growth is analysed using elasto-dynamic moving finite elements. Bucklinginduced delamination is analysed using plate/shell FE methods with growth/remeshing algorithms.     

Comparison of copper emission rates from wood treated with different preservatives to the environment

This study describes a laboratory method for the estimation of emission from preservative-treated wood in the different situations where emissions could enter the environment for use classes 3 (not in contact with ground) and 4 and 5 (in contact with the ground, fresh water or sea water) according to OECD Guidelines. Samples of scotch pine sapwood (Pinus sylvestris L.) were treated with CCA (1% and 2%), ACQ-1900 (3% and 7%), ACQ-2200 (2%), Tanalith E 3491 (2% and 2.8%), and Wolmanit CX-8 (2%).     

Primary afferent depolarizations of sensory origin within contact-sensitive mechanoreceptive afferents of a crayfish leg

Recordings from the central branches of single identified dactyl sensory afferent (DSA) neurons in a crayfish in vitro preparation were performed to study modifications of the sensory message occurring before the first central synapse. These afferents comprised hairs and force-sensitive mechanoreceptors with phasic and phasotonic response characteristics in the terminal segment (dactyl) of the crayfish leg. More than one afferent spike size was often observed in intracellular recordings from these afferents, thus indicating the presence of electrical coupling between the central processes of DSA fibers. Additionally, in identified DSA fibers with large spike sizes, primary afferent depolarizations (PADs) of up to 15 mV were observed, which sometimes triggered antidromic spikes in the afferent. Nevertheless, PADs were clearly inhibitory, because they shunted the afferent spikes. They exhibited the following properties. First, each PAD was preceded by an afferent spike from a neighboring hair, indicating that the PADs had a sensory rather than central origin. Second, PADs could follow high frequencies of afferent discharges without failure, a property suggestive of monosynaptic connections, but because PAD latencies varied by +/-0.5 ms it is more likely that they were mediated by a disynaptic pathway. Third, although PADs were evoked in an extremely reliable manner, their amplitude varied in a quantal manner. Most unitary PADs were the result of the release of < 12 quanta, the mean quantal content lying between 4 and 5; quantal size was large, approximately 1 mV. Fourth, PADs showed facilitation in some fibers, whereas in others they became much smaller when occurring at brief intervals. We suggest that PADs may be an efficient and parsimonious way to limit sensory inflow in space and time, allowing the crayfish to identify precisely both weak and strong mechanical stimuli.